11-64809769-C-G

Variant summary

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

The NM_001370259.2(MEN1):​c.341G>C​(p.Ser114Thr) 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: 31)

Consequence

MEN1
NM_001370259.2 missense

Scores

2
7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.56
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 rank MANE Protein UniProt
MEN1NM_001370259.2 linkc.341G>C p.Ser114Thr missense_variant Exon 2 of 10 ENST00000450708.7 NP_001357188.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MEN1ENST00000450708.7 linkc.341G>C p.Ser114Thr missense_variant Exon 2 of 10 5 NM_001370259.2 ENSP00000394933.3 O00255-2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Benign
23
DANN
Benign
0.93
DEOGEN2
Uncertain
0.47
T;.;.;.;.;D;D;D;D;T;.;T;.;.
Eigen
Benign
-0.083
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.90
D;D;.;.;D;.;.;D;.;D;D;D;.;D
M_CAP
Benign
0.082
D
MetaRNN
Uncertain
0.59
D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
0.97
D
MutationAssessor
Benign
0.79
.;N;N;N;N;N;N;N;N;.;.;.;.;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
0.58
N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Uncertain
0.60
Sift
Benign
0.93
T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
1.0
T;T;T;T;T;T;T;T;T;.;T;T;.;.
Polyphen
0.94, 0.054, 0.067
.;P;B;B;B;B;B;B;B;.;.;.;.;.
Vest4
0.38
MutPred
0.71
Loss of disorder (P = 0.0611);Loss of disorder (P = 0.0611);Loss of disorder (P = 0.0611);Loss of disorder (P = 0.0611);Loss of disorder (P = 0.0611);Loss of disorder (P = 0.0611);Loss of disorder (P = 0.0611);Loss of disorder (P = 0.0611);Loss of disorder (P = 0.0611);Loss of disorder (P = 0.0611);Loss of disorder (P = 0.0611);Loss of disorder (P = 0.0611);Loss of disorder (P = 0.0611);Loss of disorder (P = 0.0611);
MVP
0.88
MPC
1.0
ClinPred
0.75
D
GERP RS
5.0
Varity_R
0.50
gMVP
0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-64577241; API