rs1114167507

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_Strong

The NM_001370259.2(MEN1):​c.344G>T​(p.Arg115Leu) variant causes a missense change. 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

Scores

13
5
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.12
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 Likely_pathogenic. Variant got 7 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). GenCC has associacion of gene with multiple endocrine neoplasia type 1, pituitary gigantism, familial isolated hyperparathyroidism.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.983

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MEN1NM_001370259.2 linkuse as main transcriptc.344G>T p.Arg115Leu missense_variant 2/10 ENST00000450708.7 NP_001357188.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MEN1ENST00000450708.7 linkuse as main transcriptc.344G>T p.Arg115Leu missense_variant 2/105 NM_001370259.2 ENSP00000394933 P3O00255-2

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
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.56
D
BayesDel_noAF
Pathogenic
0.56
CADD
Pathogenic
34
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.92
D;.;.;.;.;D;D;D;D;D;.;D;.;.
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Pathogenic
0.98
D;D;.;.;D;.;.;D;.;D;D;D;.;D
M_CAP
Pathogenic
0.71
D
MetaRNN
Pathogenic
0.98
D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Uncertain
2.6
.;M;M;M;M;M;M;M;M;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-6.2
D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL
Pathogenic
0.94
Sift
Pathogenic
0.0
D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D;D;D;.;D;D;.;.
Polyphen
0.10, 1.0
.;B;D;D;D;D;D;D;D;.;.;.;.;.
Vest4
0.86
MutPred
0.88
Loss of MoRF binding (P = 0.0255);Loss of MoRF binding (P = 0.0255);Loss of MoRF binding (P = 0.0255);Loss of MoRF binding (P = 0.0255);Loss of MoRF binding (P = 0.0255);Loss of MoRF binding (P = 0.0255);Loss of MoRF binding (P = 0.0255);Loss of MoRF binding (P = 0.0255);Loss of MoRF binding (P = 0.0255);Loss of MoRF binding (P = 0.0255);Loss of MoRF binding (P = 0.0255);Loss of MoRF binding (P = 0.0255);Loss of MoRF binding (P = 0.0255);Loss of MoRF binding (P = 0.0255);
MVP
1.0
MPC
2.4
ClinPred
1.0
D
GERP RS
5.0
Varity_R
0.96
gMVP
0.98

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr11-64577238; API