chr17-62059724-T-C

Position:

• chr17-62059724-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005121.3(MED13):​c.301+3343A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,968 control chromosomes in the GnomAD database, including 13,452 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 0.38 (13452 hom., cov: 32)
• Consequence: MED13 NM_005121.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED13	NM_005121.3	c.301+3343A>G		intron_variant		ENST00000397786.7	NP_005112.2
MED13	XM_011525551.3	c.301+3343A>G		intron_variant			XP_011523853.1
MED13	XM_011525552.3	c.301+3343A>G		intron_variant			XP_011523854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED13	ENST00000397786.7	c.301+3343A>G		intron_variant		1	NM_005121.3	ENSP00000380888.2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57414 AN: 151850 Hom.: 13402 Cov.: 32

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.336

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.379 AC: 57525 AN: 151968 Hom.: 13452 Cov.: 32 AF XY: 0.386 AC XY: 28680 AN XY: 74272

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.725

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.343

Alfa AF: 0.249 Hom.: 5674

Bravo AF: 0.384

Asia WGS AF: 0.573 AC: 1991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Benign	0.78

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: rs4968469; hg19: chr17-60137085;