NM_005121.3:c.6117+349G>C

Variant names:

• chr17-61952616-C-G
• rs12941827
• NM_005121.3:c.6117+349G>C

Variant summary

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

The NM_005121.3(MED13):​c.6117+349G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,144 control chromosomes in the GnomAD database, including 1,997 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 (1997 hom., cov: 32)
• Consequence: MED13 NM_005121.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.780
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED13	NM_005121.3	c.6117+349G>C		intron_variant	Intron 27 of 29	ENST00000397786.7	NP_005112.2
MED13	XM_011525551.3	c.5958+349G>C		intron_variant	Intron 26 of 28		XP_011523853.1
MED13	XM_011525553.4	c.5448+349G>C		intron_variant	Intron 24 of 26		XP_011523855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED13	ENST00000397786.7	c.6117+349G>C		intron_variant	Intron 27 of 29	1	NM_005121.3	ENSP00000380888.2

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23778 AN: 152026 Hom.: 1999 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0645

Gnomad SAS AF: 0.0803

Gnomad FIN AF: 0.0907

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.156 AC: 23779 AN: 152144 Hom.: 1997 Cov.: 32 AF XY: 0.151 AC XY: 11226 AN XY: 74392

African (AFR) AF: 0.177 AC: 7354 AN: 41484

American (AMR) AF: 0.161 AC: 2466 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 716 AN: 3468

East Asian (EAS) AF: 0.0645 AC: 334 AN: 5180

South Asian (SAS) AF: 0.0799 AC: 385 AN: 4818

European-Finnish (FIN) AF: 0.0907 AC: 960 AN: 10582

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10954 AN: 68004

Other (OTH) AF: 0.192 AC: 404 AN: 2108

Alfa AF: 0.149 Hom.: 234

Bravo AF: 0.168

Asia WGS AF: 0.0880 AC: 308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.20
DANN	Benign	0.61
PhyloP100		-0.78
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: rs12941827; hg19: chr17-60029977;