chr11-93784708-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004268.5(MED17):c.195C>G(p.Gly65Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 1,548,836 control chromosomes in the GnomAD database, including 303,143 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G65G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.56 ( 25261 hom., cov: 33)

Exomes 𝑓: 0.63 ( 277882 hom. )

Consequence

MED17
NM_004268.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.202

Publications

22 publications found

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 Gene-Disease associations (from GenCC):

infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

MED17 links:

ENSG00000284057 (HGNC:):

ENSG00000284057 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 11-93784708-C-G is Benign according to our data. Variant chr11-93784708-C-G is described in ClinVar as [Benign]. Clinvar id is 129600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.202 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED17	NM_004268.5 link	c.195C>G	p.Gly65Gly	synonymous_variant	Exon 1 of 12	ENST00000251871.9	NP_004259.3	Q9NVC6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED17	ENST00000251871.9 link	c.195C>G	p.Gly65Gly	synonymous_variant	Exon 1 of 12	1	NM_004268.5	ENSP00000251871.3		Q9NVC6-1
ENSG00000284057	ENST00000638767.1 link	c.756C>G	p.Gly252Gly	synonymous_variant	Exon 8 of 19	5		ENSP00000492220.1		A0A1W2PRB8

Frequencies

GnomAD3 genomes

AF:

0.559

AC:

84705

AN:

151528

Hom.:

25248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.334

Gnomad AMI

AF:

0.574

Gnomad AMR

AF:

0.704

Gnomad ASJ

AF:

0.590

Gnomad EAS

AF:

0.748

Gnomad SAS

AF:

0.594

Gnomad FIN

AF:

0.668

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.627

Gnomad OTH

AF:

0.585

GnomAD2 exomes

AF:

0.645

AC:

99008

AN:

153594

AF XY:

0.641

show subpopulations

Gnomad AFR exome

AF:

0.330

Gnomad AMR exome

AF:

0.793

Gnomad ASJ exome

AF:

0.583

Gnomad EAS exome

AF:

0.750

Gnomad FIN exome

AF:

0.669

Gnomad NFE exome

AF:

0.632

Gnomad OTH exome

AF:

0.615

GnomAD4 exome

AF:

0.627

AC:

875994

AN:

1397190

Hom.:

277882

Cov.:

AF XY:

0.627

AC XY:

432320

AN XY:

689594

show subpopulations

African (AFR)

AF:

0.324

AC:

10406

AN:

32156

American (AMR)

AF:

0.780

AC:

27890

AN:

35768

Ashkenazi Jewish (ASJ)

AF:

0.585

AC:

14725

AN:

25178

East Asian (EAS)

AF:

0.763

AC:

27803

AN:

36452

South Asian (SAS)

AF:

0.598

AC:

47600

AN:

79556

European-Finnish (FIN)

AF:

0.658

AC:

28519

AN:

43352

Middle Eastern (MID)

AF:

0.588

AC:

3236

AN:

5504

European-Non Finnish (NFE)

AF:

0.629

AC:

680129

AN:

1081094

Other (OTH)

AF:

0.614

AC:

35686

AN:

58130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

18936

37871

56807

75742

94678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.559

AC:

84744

AN:

151646

Hom.:

25261

Cov.:

AF XY:

0.564

AC XY:

41815

AN XY:

74076

show subpopulations

African (AFR)

AF:

0.334

AC:

13802

AN:

41370

American (AMR)

AF:

0.704

AC:

10746

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.590

AC:

2046

AN:

3466

East Asian (EAS)

AF:

0.748

AC:

3840

AN:

5132

South Asian (SAS)

AF:

0.596

AC:

2874

AN:

4826

European-Finnish (FIN)

AF:

0.668

AC:

7017

AN:

10500

Middle Eastern (MID)

AF:

0.568

AC:

166

AN:

292

European-Non Finnish (NFE)

AF:

0.627

AC:

42503

AN:

67788

Other (OTH)

AF:

0.582

AC:

1229

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1815

3630

5444

7259

9074

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.576

Hom.:

6639

Bravo

AF:

0.553

Asia WGS

AF:

0.609

AC:

2118

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly

Benign:4

Jun 28, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 18, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 07, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 28, 2012

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

-0.20

PromoterAI

-0.014

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr11-93784708-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over