rs2302777

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014815.4(MED24):​c.2142T>G​(p.Ile714Met) 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 benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I714I) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

MED24
NM_014815.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.417
Variant links:
Genes affected
MED24 (HGNC:22963): (mediator complex subunit 24) This gene encodes a component of the mediator complex (also known as TRAP, SMCC, DRIP, or ARC), a transcriptional coactivator complex thought to be required for the expression of almost all genes. The mediator complex is recruited by transcriptional activators or nuclear receptors to induce gene expression, possibly by interacting with RNA polymerase II and promoting the formation of a transcriptional pre-initiation complex. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08031961).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MED24NM_014815.4 linkuse as main transcriptc.2142T>G p.Ile714Met missense_variant 20/26 ENST00000394128.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MED24ENST00000394128.7 linkuse as main transcriptc.2142T>G p.Ile714Met missense_variant 20/261 NM_014815.4 P1O75448-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
68
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
10
DANN
Benign
0.85
DEOGEN2
Benign
0.25
.;.;T;.;T;T
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.066
N
LIST_S2
Benign
0.78
T;.;T;T;T;T
M_CAP
Benign
0.0062
T
MetaRNN
Benign
0.080
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
.;.;N;.;.;.
MutationTaster
Benign
0.95
P;P;P;P;P;P;P
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-1.1
.;.;N;N;.;N
REVEL
Benign
0.039
Sift
Benign
0.043
.;.;D;D;.;D
Sift4G
Benign
0.086
T;T;T;T;T;T
Polyphen
0.0, 0.0010
.;B;B;B;.;B
Vest4
0.18
MutPred
0.22
.;.;Gain of catalytic residue at V710 (P = 0.0534);.;.;.;
MVP
0.15
MPC
0.35
ClinPred
0.23
T
GERP RS
1.1
Varity_R
0.066
gMVP
0.46

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: rs2302777; hg19: chr17-38179492; API