rs9889324

Variant names:

• chr17-62049261-C-A
• rs9889324
• NM_005121.3:c.470+3276G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-62049261-C-A
• chr17-62049261-C-G
• chr17-62049261-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005121.3(MED13):​c.470+3276G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,654 control chromosomes in the GnomAD database, including 12,550 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 0.37 (12550 hom., cov: 30)
• Consequence: MED13 NM_005121.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED13	NM_005121.3	c.470+3276G>T		intron_variant	Intron 3 of 29	ENST00000397786.7	NP_005112.2
MED13	XM_011525551.3	c.470+3276G>T		intron_variant	Intron 3 of 28		XP_011523853.1
MED13	XM_011525552.3	c.470+3276G>T		intron_variant	Intron 3 of 26		XP_011523854.1
MED13	XM_011525553.4	c.-54+3276G>T		intron_variant	Intron 1 of 26		XP_011523855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED13	ENST00000397786.7	c.470+3276G>T		intron_variant	Intron 3 of 29	1	NM_005121.3	ENSP00000380888.2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55891 AN: 151538 Hom.: 12513 Cov.: 30

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.369 AC: 55986 AN: 151654 Hom.: 12550 Cov.: 30 AF XY: 0.377 AC XY: 27926 AN XY: 74122

African (AFR) AF: 0.595 AC: 24571 AN: 41292

American (AMR) AF: 0.284 AC: 4335 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 951 AN: 3470

East Asian (EAS) AF: 0.722 AC: 3707 AN: 5132

South Asian (SAS) AF: 0.465 AC: 2232 AN: 4804

European-Finnish (FIN) AF: 0.365 AC: 3827 AN: 10474

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

European-Non Finnish (NFE) AF: 0.226 AC: 15369 AN: 67922

Other (OTH) AF: 0.337 AC: 710 AN: 2106

Alfa AF: 0.246 Hom.: 3333

Bravo AF: 0.373

Asia WGS AF: 0.561 AC: 1952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.90
DANN	Benign	0.19
PhyloP100		0.19
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: rs9889324; hg19: chr17-60126622;