17-61985231-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005121.3(MED13):c.2386-141A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 606,332 control chromosomes in the GnomAD database, including 11,779 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2412 hom., cov: 32)
  • Exomes 𝑓: 0.18 (9367 hom.)
• Consequence: MED13 NM_005121.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130

Genes affected

MED13 (HGNC:22474): (mediator complex subunit 13) 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. The product of this gene is proposed to form a sub-complex with MED12, cyclin C, and CDK8 that can negatively regulate transactivation by mediator. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED13	NM_005121.3	c.2386-141A>G		intron_variant		ENST00000397786.7
MED13	XM_011525551.3	c.2386-141A>G		intron_variant
MED13	XM_011525552.3	c.2386-141A>G		intron_variant
MED13	XM_011525553.4	c.1717-141A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED13	ENST00000397786.7	c.2386-141A>G		intron_variant		1	NM_005121.3	P1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24440 AN: 152132 Hom.: 2408 Cov.: 32

Gnomad AFR AF: 0.0919

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.183 AC: 83021 AN: 454082 Hom.: 9367 AF XY: 0.180 AC XY: 43020 AN XY: 238750

Gnomad4 AFR exome AF: 0.0932

Gnomad4 AMR exome AF: 0.175

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.464

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.262

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.161 AC: 24459 AN: 152250 Hom.: 2412 Cov.: 32 AF XY: 0.167 AC XY: 12413 AN XY: 74428

Gnomad4 AFR AF: 0.0919

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.170

Alfa AF: 0.149 Hom.: 480

Bravo AF: 0.154

Asia WGS AF: 0.301 AC: 1046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	11
Dann	Benign	0.86

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

Other links and lift over

dbSNP: rs16945753; hg19: chr17-60062592;