NM_001370259.2:c.1522C>G
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 5P and 2B. PM2PM5PP2BP4_Moderate
The NM_001370259.2(MEN1):c.1522C>G(p.Gln508Glu) variant causes a missense change. 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 Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q508K) has been classified as Pathogenic.
Frequency
Genomes: not found (cov: 34)
Consequence
MEN1
NM_001370259.2 missense
NM_001370259.2 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 4.98
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;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr11-64804645-G-T is described in Lovd as [Pathogenic].
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.
BP4
Computational evidence support a benign effect (MetaRNN=0.19269654).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MEN1 | NM_001370259.2 | c.1522C>G | p.Gln508Glu | missense_variant | Exon 10 of 10 | ENST00000450708.7 | NP_001357188.2 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
34
GnomAD4 exome Cov.: 43
GnomAD4 exome
Cov.:
43
GnomAD4 genome
GnomAD4 genome
Cov.:
34
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not provided Uncertain:1
Jul 13, 2012
Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: research
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.;.;.;T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;.;.;T;.;.;T;.
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
.;.;.;.;.;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T;T
Polyphen
0.0
.;B;B;B;B;B;B;B;B
Vest4
MutPred
0.43
.;.;.;.;.;Loss of MoRF binding (P = 0.0394);Loss of MoRF binding (P = 0.0394);Loss of MoRF binding (P = 0.0394);Loss of MoRF binding (P = 0.0394);
MVP
MPC
2.1
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at