17-61952970-C-T

Position:

chr17-61952970-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBS1BS2

The NM_005121.3(MED13):c.6112G>A(p.Gly2038Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000279 in 1,612,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

MED13
NM_005121.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.69

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MED13. . Gene score misZ 2.6232 (greater than the threshold 3.09). Trascript score misZ 3.3083 (greater than threshold 3.09). GenCC has associacion of gene with syndromic intellectual disability, intellectual developmental disorder 61, complex neurodevelopmental disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.05202967).

BP6

Variant 17-61952970-C-T is Benign according to our data. Variant chr17-61952970-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2461993.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0000658 (10/152076) while in subpopulation AFR AF= 0.000193 (8/41408). AF 95% confidence interval is 0.0000957. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MED13	NM_005121.3 linkuse as main transcript	c.6112G>A	p.Gly2038Ser	missense_variant	27/30	ENST00000397786.7
MED13	XM_011525551.3 linkuse as main transcript	c.5953G>A	p.Gly1985Ser	missense_variant	26/29
MED13	XM_011525553.4 linkuse as main transcript	c.5443G>A	p.Gly1815Ser	missense_variant	24/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED13	ENST00000397786.7 linkuse as main transcript	c.6112G>A	p.Gly2038Ser	missense_variant	27/30	1	NM_005121.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000113

AC:

AN:

247510

Hom.:

AF XY:

0.0000595

AC XY:

AN XY:

134368

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000676

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000334

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1460152

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726444

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000677

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000658

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000323

Hom.:

Bravo

AF:

0.0000567

ESP6500AA

AF:

0.000265

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000149

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.23

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.051

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.22

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.050

REVEL

Uncertain

0.30

Sift

Benign

0.20

Sift4G

Benign

0.47

Polyphen

0.0010

Vest4

0.18

MVP

0.25

MPC

1.8

ClinPred

0.033

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.050

gMVP

0.33

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over