11-93795026-G-C

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.978G>C(p.Val326Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 1,614,080 control chromosomes in the GnomAD database, including 123 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. V326V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0035 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 110 hom. )

Consequence

MED17
NM_004268.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.309

Publications

5 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=-0.44).

BP6

Variant 11-93795026-G-C is Benign according to our data. Variant chr11-93795026-G-C is described in CliVar as Benign. Clinvar id is 129606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-93795026-G-C is described in CliVar as Benign. Clinvar id is 129606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-93795026-G-C is described in CliVar as Benign. Clinvar id is 129606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-93795026-G-C is described in CliVar as Benign. Clinvar id is 129606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-93795026-G-C is described in CliVar as Benign. Clinvar id is 129606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-93795026-G-C is described in CliVar as Benign. Clinvar id is 129606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-93795026-G-C is described in CliVar as Benign. Clinvar id is 129606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-93795026-G-C is described in CliVar as Benign. Clinvar id is 129606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-93795026-G-C is described in CliVar as Benign. Clinvar id is 129606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-93795026-G-C is described in CliVar as Benign. Clinvar id is 129606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-93795026-G-C is described in CliVar as Benign. Clinvar id is 129606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.309 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED17	NM_004268.5 link	c.978G>C	p.Val326Val	synonymous_variant	Exon 6 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.978G>C	p.Val326Val	synonymous_variant	Exon 6 of 12	1	NM_004268.5	ENSP00000251871.3		Q9NVC6-1
ENSG00000284057	ENST00000638767.1 link	c.1539G>C	p.Val513Val	synonymous_variant	Exon 13 of 19	5		ENSP00000492220.1		A0A1W2PRB8

Frequencies

GnomAD3 genomes

AF:

0.00354

AC:

538

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00509

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0571

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00555

AC:

1395

AN:

251404

AF XY:

0.00509

show subpopulations

Gnomad AFR exome

AF:

0.00474

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0678

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00237

AC:

3458

AN:

1461860

Hom.:

110

Cov.:

AF XY:

0.00225

AC XY:

1635

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.00594

AC:

199

AN:

33478

American (AMR)

AF:

0.000268

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0744

AC:

2954

AN:

39690

South Asian (SAS)

AF:

0.000846

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000324

AC:

AN:

1112002

Other (OTH)

AF:

0.00295

AC:

178

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

200

399

599

798

998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00354

AC:

539

AN:

152220

Hom.:

Cov.:

AF XY:

0.00370

AC XY:

275

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00510

AC:

212

AN:

41538

American (AMR)

AF:

0.00105

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0572

AC:

296

AN:

5176

South Asian (SAS)

AF:

0.00145

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68012

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

101

126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000380

Hom.:

Bravo

AF:

0.00432

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 21, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

May 24, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly

Benign:1

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.1

(source)

DANN

Benign

0.73

PhyloP100

0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=92/8

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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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