Variant 17-40022808-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014815.4(MED24):c.2269C>G(p.Arg757Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000185 in 1,613,300 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

MED24
NM_014815.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.67

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]

MED24 links:

MED24 (HGNC:):

MED24 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED24	NM_014815.4 linkuse as main transcript	c.2269C>G	p.Arg757Gly	missense_variant	21/26	ENST00000394128.7	NP_055630.2	O75448-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED24	ENST00000394128.7 linkuse as main transcript	c.2269C>G	p.Arg757Gly	missense_variant	21/26	1	NM_014815.4	ENSP00000377686.2		O75448-1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000600

AC:

AN:

250196

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000196

AC:

286

AN:

1461236

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

119

AN XY:

726908

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000243

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152064

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.0000793

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2022

The c.2269C>G (p.R757G) alteration is located in exon 21 (coding exon 20) of the MED24 gene. This alteration results from a C to G substitution at nucleotide position 2269, causing the arginine (R) at amino acid position 757 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Uncertain

0.061

BayesDel_noAF

Uncertain

0.10

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.29

.;.;T;.;.;T;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;.;D;D;D;D;D

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.59

D;D;D;D;D;D;D

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.4

.;.;M;.;.;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.3

.;.;N;N;.;.;N

REVEL

Benign

0.27

Sift

Benign

0.13

.;.;T;T;.;.;T

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D

Polyphen

0.87, 0.90

.;P;P;P;.;.;.

Vest4

0.89

MVP

0.66

MPC

0.91

ClinPred

0.53

GERP RS

4.9

Varity_R

0.27

gMVP

0.69

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over