chr11-64804733-G-C

Variant names:

• chr11-64804733-G-C
• rs200280309
• NM_001370259.2:c.1434C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001370259.2(MEN1):​c.1434C>G​(p.Gly478Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G478G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: MEN1 NM_001370259.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0640
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 11-64804733-G-C is Benign according to our data. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64804733-G-C is described in CliVar as Likely_benign. Clinvar id is 1668927.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.064 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEN1	NM_001370259.2	c.1434C>G	p.Gly478Gly	synonymous_variant	Exon 10 of 10	ENST00000450708.7	NP_001357188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEN1	ENST00000450708.7	c.1434C>G	p.Gly478Gly	synonymous_variant	Exon 10 of 10	5	NM_001370259.2	ENSP00000394933.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 34

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Multiple endocrine neoplasia, type 1 Benign:1

Jun 25, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.9
DANN	Benign	0.79
PhyloP100		-0.064

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

Other links and lift over

dbSNP: rs200280309; hg19: chr11-64572205;