rs4968469

Variant names:

• chr17-62059724-T-C
• rs4968469
• NM_005121.3:c.301+3343A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-62059724-T-C
• chr17-62059724-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

MED13 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual developmental disorder 61

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae), G2P
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MED13	NM_005121.3	c.301+3343A>G		intron_variant	Intron 2 of 29	ENST00000397786.7	NP_005112.2
MED13	XM_011525551.3	c.301+3343A>G		intron_variant	Intron 2 of 28		XP_011523853.1
MED13	XM_011525552.3	c.301+3343A>G		intron_variant	Intron 2 of 26		XP_011523854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED13	ENST00000397786.7	c.301+3343A>G		intron_variant	Intron 2 of 29	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

African (AFR) AF: 0.625 AC: 25914 AN: 41456

American (AMR) AF: 0.289 AC: 4405 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 952 AN: 3466

East Asian (EAS) AF: 0.725 AC: 3746 AN: 5166

South Asian (SAS) AF: 0.465 AC: 2238 AN: 4808

European-Finnish (FIN) AF: 0.367 AC: 3876 AN: 10552

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15389 AN: 67950

Other (OTH) AF: 0.343 AC: 722 AN: 2108

Alfa AF: 0.281 Hom.: 21784

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
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs4968469; hg19: chr17-60137085;