17-40023239-A-T

Variant names:

• chr17-40023239-A-T
• rs2302777
• NM_014815.4:c.2142T>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014815.4(MED24):​c.2142T>A​(p.Ile714Ile) variant causes a synonymous 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. 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 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417
• Publications: 53 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-0.417 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014815.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED24	NM_014815.4	MANE Select	c.2142T>A	p.Ile714Ile	synonymous	Exon 20 of 26	NP_055630.2
	MED24	NM_001330211.2		c.2199T>A	p.Ile733Ile	synonymous	Exon 21 of 27	NP_001317140.1	F5GY88
	MED24	NM_001079518.2		c.2103T>A	p.Ile701Ile	synonymous	Exon 19 of 25	NP_001072986.1	O75448-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED24	ENST00000394128.7	TSL:1 MANE Select	c.2142T>A	p.Ile714Ile	synonymous	Exon 20 of 26	ENSP00000377686.2	O75448-1
	MED24	ENST00000394126.5	TSL:1	c.2217T>A	p.Ile739Ile	synonymous	Exon 19 of 25	ENSP00000377684.1	A0A0B4J1W0
	MED24	ENST00000887917.1		c.2235T>A	p.Ile745Ile	synonymous	Exon 21 of 27	ENSP00000557976.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 68

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.5
DANN	Benign	0.87
PhyloP100		-0.42
PromoterAI		-0.0051	Neutral

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

Other links and lift over

dbSNP: rs2302777; hg19: chr17-38179492;