NM_001370259.2:c.1522C>T

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_001370259.2(MEN1):​c.1522C>T​(p.Gln508*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 34)

Consequence

MEN1
NM_001370259.2 stop_gained

Scores

2
2
3

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 4.98

Publications

2 publications found
Variant links:
Genes affected
MEN1 (HGNC:7010): (menin 1) This gene encodes menin, a tumor suppressor associated with a syndrome known as multiple endocrine neoplasia type 1. Menin is a scaffold protein that functions in histone modification and epigenetic gene regulation. It is thought to regulate several pathways and processes by altering chromatin structure through the modification of histones. [provided by RefSeq, May 2019]
MEN1 Gene-Disease associations (from GenCC):
  • multiple endocrine neoplasia type 1
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet, Ambry Genetics
  • familial isolated hyperparathyroidism
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • pituitary gigantism
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • hereditary pheochromocytoma-paraganglioma
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 12 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 64 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 11-64804645-G-A is Pathogenic according to our data. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804645-G-A is described in CliVar as Pathogenic. Clinvar id is 931033.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MEN1NM_001370259.2 linkc.1522C>T p.Gln508* stop_gained Exon 10 of 10 ENST00000450708.7 NP_001357188.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MEN1ENST00000450708.7 linkc.1522C>T p.Gln508* stop_gained Exon 10 of 10 5 NM_001370259.2 ENSP00000394933.3 O00255-2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
43
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Multiple endocrine neoplasia, type 1 Pathogenic:1
Mar 31, 2019
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP4. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.62
D
BayesDel_noAF
Pathogenic
0.36
CADD
Pathogenic
36
DANN
Uncertain
0.99
Eigen
Uncertain
0.33
Eigen_PC
Benign
0.025
FATHMM_MKL
Benign
0.51
D
PhyloP100
5.0
Vest4
0.80
GERP RS
4.1
Mutation Taster
=0/200
disease causing (ClinVar)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs386833403; hg19: chr11-64572117; COSMIC: COSV53644993; COSMIC: COSV53644993; API