17-61985231-T-C

Variant names:

• chr17-61985231-T-C
• rs16945753
• NM_005121.3:c.2386-141A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005121.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED13	NM_005121.3	MANE Select	c.2386-141A>G		intron	N/A	NP_005112.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED13	ENST00000397786.7	TSL:1 MANE Select	c.2386-141A>G		intron	N/A	ENSP00000380888.2

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

African (AFR) AF: 0.0932 AC: 1134 AN: 12162

American (AMR) AF: 0.175 AC: 2891 AN: 16506

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 2132 AN: 13470

East Asian (EAS) AF: 0.464 AC: 14184 AN: 30570

South Asian (SAS) AF: 0.152 AC: 5896 AN: 38906

European-Finnish (FIN) AF: 0.262 AC: 8092 AN: 30920

Middle Eastern (MID) AF: 0.124 AC: 260 AN: 2100

European-Non Finnish (NFE) AF: 0.154 AC: 43801 AN: 283636

Other (OTH) AF: 0.179 AC: 4631 AN: 25812

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

African (AFR) AF: 0.0919 AC: 3822 AN: 41578

American (AMR) AF: 0.168 AC: 2561 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 546 AN: 3468

East Asian (EAS) AF: 0.498 AC: 2575 AN: 5172

South Asian (SAS) AF: 0.159 AC: 765 AN: 4826

European-Finnish (FIN) AF: 0.275 AC: 2908 AN: 10582

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10836 AN: 68024

Other (OTH) AF: 0.170 AC: 360 AN: 2112

Alfa AF: 0.160 Hom.: 1307

Bravo AF: 0.154

Asia WGS AF: 0.301 AC: 1046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		0.013
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: rs16945753; hg19: chr17-60062592;