rs2848477

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004268.5(MED17):c.207G>C(p.Glu69Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 1,546,188 control chromosomes in the GnomAD database, including 302,643 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 25275 hom., cov: 33)

Exomes 𝑓: 0.63 ( 277368 hom. )

Consequence

MED17
NM_004268.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.209

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3689065E-6).

BP6

Variant 11-93784720-G-C is Benign according to our data. Variant chr11-93784720-G-C is described in ClinVar as [Benign]. Clinvar id is 129601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-93784720-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 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.207G>C	p.Glu69Asp	missense_variant	1/12	ENST00000251871.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED17	ENST00000251871.9 linkuse as main transcript	c.207G>C	p.Glu69Asp	missense_variant	1/12	1	NM_004268.5	P1	Q9NVC6-1

Frequencies

GnomAD3 genomes

AF:

0.559

AC:

84751

AN:

151632

Hom.:

25262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.334

Gnomad AMI

AF:

0.575

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:

0.573

Gnomad NFE

AF:

0.627

Gnomad OTH

AF:

0.585

GnomAD3 exomes

AF:

0.646

AC:

97056

AN:

150320

Hom.:

32277

AF XY:

0.642

AC XY:

51847

AN XY:

80760

show subpopulations

Gnomad AFR exome

AF:

0.333

Gnomad AMR exome

AF:

0.793

Gnomad ASJ exome

AF:

0.583

Gnomad EAS exome

AF:

0.751

Gnomad SAS exome

AF:

0.596

Gnomad FIN exome

AF:

0.673

Gnomad NFE exome

AF:

0.632

Gnomad OTH exome

AF:

0.618

GnomAD4 exome

AF:

0.627

AC:

874344

AN:

1394438

Hom.:

277368

Cov.:

AF XY:

0.627

AC XY:

431532

AN XY:

688248

show subpopulations

Gnomad4 AFR exome

AF:

0.324

Gnomad4 AMR exome

AF:

0.780

Gnomad4 ASJ exome

AF:

0.585

Gnomad4 EAS exome

AF:

0.763

Gnomad4 SAS exome

AF:

0.598

Gnomad4 FIN exome

AF:

0.658

Gnomad4 NFE exome

AF:

0.629

Gnomad4 OTH exome

AF:

0.614

GnomAD4 genome

AF:

0.559

AC:

84790

AN:

151750

Hom.:

25275

Cov.:

AF XY:

0.564

AC XY:

41835

AN XY:

74134

show subpopulations

Gnomad4 AFR

AF:

0.334

Gnomad4 AMR

AF:

0.704

Gnomad4 ASJ

AF:

0.590

Gnomad4 EAS

AF:

0.749

Gnomad4 SAS

AF:

0.596

Gnomad4 FIN

AF:

0.668

Gnomad4 NFE

AF:

0.627

Gnomad4 OTH

AF:

0.582

Alfa

AF:

0.601

Hom.:

8245

Bravo

AF:

0.554

TwinsUK

AF:

0.634

AC:

2351

ALSPAC

AF:

0.634

AC:

2444

ESP6500AA

AF:

0.369

AC:

1525

ESP6500EA

AF:

0.642

AC:

5300

ExAC

AF:

0.544

AC:

49987

Asia WGS

AF:

0.611

AC:

2122

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

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	May 31, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 18, 2019	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Dec 28, 2012	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.054

.;T;.;.;.;.;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.22

T;T;T;T;T;T;T

MetaRNN

Benign

0.0000024

T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

.;L;.;.;.;.;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.20

.;N;.;N;.;.;.

REVEL

Benign

0.19

Sift

Benign

0.87

.;T;.;T;.;.;.

Sift4G

Benign

0.44

.;T;.;T;.;.;.

Polyphen

0.0

.;B;.;.;.;.;.

Vest4

0.018

MutPred

0.40

.;Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);

MPC

0.25

ClinPred

0.0029

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.075

gMVP

0.24

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