Variant rs36120755 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004268.5(MED17):c.1260A>G(p.Ser420=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00615 in 1,613,904 control chromosomes in the GnomAD database, including 531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 281 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 250 hom. )

Consequence

MED17
NM_004268.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.120

Variant links:

Genes affected

MED17 (HGNC:2375): (mediator complex subunit 17) The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. [provided by RefSeq, Jul 2008]

MED17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 11-93797651-A-G is Benign according to our data. Variant chr11-93797651-A-G is described in ClinVar as [Benign]. Clinvar id is 129598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-93797651-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED17	NM_004268.5 linkuse as main transcript	c.1260A>G	p.Ser420=	synonymous_variant	8/12	ENST00000251871.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED17	ENST00000251871.9 linkuse as main transcript	c.1260A>G	p.Ser420=	synonymous_variant	8/12	1	NM_004268.5	P1	Q9NVC6-1

Frequencies

GnomAD3 genomes

AF:

0.0333

AC:

5071

AN:

152172

Hom.:

280

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0110

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.00832

AC:

2090

AN:

251266

Hom.:

110

AF XY:

0.00604

AC XY:

821

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.115

Gnomad AMR exome

AF:

0.00463

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00331

AC:

4832

AN:

1461616

Hom.:

250

Cov.:

AF XY:

0.00277

AC XY:

2016

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.00503

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000152

Gnomad4 OTH exome

AF:

0.00762

GnomAD4 genome

AF:

0.0334

AC:

5091

AN:

152288

Hom.:

281

Cov.:

AF XY:

0.0324

AC XY:

2410

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.0175

Hom.:

Bravo

AF:

0.0378

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 31, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 10, 2013

- -

Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.0

DANN

Benign

0.76

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