chr11-64809735-T-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_001370259.2(MEN1):c.375A>G(p.Ile125Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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
NM_001370259.2 missense
Scores
9
7
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.14
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 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MEN1. . Trascript score misZ: 4.1921 (greater than threshold 3.09). The gene has 113 curated pathogenic missense variants (we use a threshold of 10). The gene has 20 curated benign missense variants. GenCC has associacion of the gene with multiple endocrine neoplasia type 1, pituitary gigantism, familial isolated hyperparathyroidism.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.892
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MEN1 | NM_001370259.2 | c.375A>G | p.Ile125Met | missense_variant | 2/10 | ENST00000450708.7 | NP_001357188.2 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;.;.;.;D;D;D;D;D;.;D;.;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;.;.;D;.;.;D;.;D;D;D;.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
.;M;M;M;M;M;M;M;M;.;.;.;.;.
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
N;N;N;N;N;N;N;N;N;N;N;N;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D;.;D;D;.;.
Polyphen
1.0, 1.0, 1.0
.;D;D;D;D;D;D;D;D;.;.;.;.;.
Vest4
MutPred
Gain of catalytic residue at V121 (P = 0.0419);Gain of catalytic residue at V121 (P = 0.0419);Gain of catalytic residue at V121 (P = 0.0419);Gain of catalytic residue at V121 (P = 0.0419);Gain of catalytic residue at V121 (P = 0.0419);Gain of catalytic residue at V121 (P = 0.0419);Gain of catalytic residue at V121 (P = 0.0419);Gain of catalytic residue at V121 (P = 0.0419);Gain of catalytic residue at V121 (P = 0.0419);Gain of catalytic residue at V121 (P = 0.0419);Gain of catalytic residue at V121 (P = 0.0419);Gain of catalytic residue at V121 (P = 0.0419);Gain of catalytic residue at V121 (P = 0.0419);Gain of catalytic residue at V121 (P = 0.0419);
MVP
MPC
2.2
ClinPred
D
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
Publications
No publications associated with this variant yet.