17-40019641-G-C

Variant names:

• chr17-40019641-G-C
• NM_014815.4:c.2858C>G

Variant summary

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

The NM_014815.4(MED24):​c.2858C>G​(p.Ser953Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,858 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MED24 NM_014815.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.00

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]

ACMG classification

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 rank	MANE	Protein	UniProt
MED24	NM_014815.4	c.2858C>G	p.Ser953Trp	missense_variant	Exon 26 of 26	ENST00000394128.7	NP_055630.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED24	ENST00000394128.7	c.2858C>G	p.Ser953Trp	missense_variant	Exon 26 of 26	1	NM_014815.4	ENSP00000377686.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439858 Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 713054

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: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	35
DANN	Benign	0.92
DEOGEN2	Benign	0.37	.;.;T;.;.;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.99	D;.;D;D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.67	D;D;D;D;D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.4	.;.;M;.;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.1	.;.;D;D;.;.
REVEL	Uncertain	0.44
Sift	Uncertain	0.0010	.;.;D;D;.;.
Sift4G	Uncertain	0.010	D;D;D;D;D;D
Polyphen		1.0, 1.0	.;D;D;D;.;.
Vest4		0.65
MutPred		0.44		.;.;Loss of disorder (P = 0.0204);.;.;.;
MVP		0.61
MPC		1.3
ClinPred		0.99	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-38175894;