chr11-64804770-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_001370259.2(MEN1):ā€‹c.1397A>Cā€‹(p.Glu466Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MEN1
NM_001370259.2 missense

Scores

1
9
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.59
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the MEN1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 113 curated pathogenic missense variants (we use a threshold of 10). The gene has 20 curated benign missense variants. Trascript score misZ: 4.1921 (above the threshold of 3.09). GenCC associations: The gene is linked to multiple endocrine neoplasia type 1, pituitary gigantism, familial isolated hyperparathyroidism.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MEN1NM_001370259.2 linkc.1397A>C p.Glu466Ala missense_variant 10/10 ENST00000450708.7 NP_001357188.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MEN1ENST00000450708.7 linkc.1397A>C p.Glu466Ala missense_variant 10/105 NM_001370259.2 ENSP00000394933.3 O00255-2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1444074
Hom.:
0
Cov.:
43
AF XY:
0.00
AC XY:
0
AN XY:
718604
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.060
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.31
T;.;.;.;.;D;D;D;D
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.11
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.87
D;D;.;.;D;.;.;D;.
M_CAP
Pathogenic
0.87
D
MetaRNN
Uncertain
0.47
T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
0.73
D
MutationAssessor
Benign
1.2
.;.;.;.;.;L;L;L;L
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-1.5
N;N;N;N;N;N;N;N;N
REVEL
Uncertain
0.47
Sift
Benign
0.078
T;T;T;T;T;T;T;T;T
Sift4G
Benign
0.31
T;T;T;T;T;T;T;T;T
Polyphen
0.34, 0.39
.;B;B;B;B;B;B;B;B
Vest4
0.29
MutPred
0.55
.;.;.;.;.;Loss of solvent accessibility (P = 0.0224);Loss of solvent accessibility (P = 0.0224);Loss of solvent accessibility (P = 0.0224);Loss of solvent accessibility (P = 0.0224);
MVP
0.69
MPC
1.4
ClinPred
0.73
D
GERP RS
4.5
Varity_R
0.076
gMVP
0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1352053477; hg19: chr11-64572242; API