rs2848477

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

33 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 -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 VariationId is 129601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
MED17	NM_004268.5 link	c.207G>C	p.Glu69Asp	missense_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.207G>C	p.Glu69Asp	missense_variant	Exon 1 of 12	1	NM_004268.5	ENSP00000251871.3		Q9NVC6-1
ENSG00000284057	ENST00000638767.1 link	c.768G>C	p.Glu256Asp	missense_variant	Exon 8 of 19	5		ENSP00000492220.1		A0A1W2PRB8

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

GnomAD2 exomes

AF:

0.646

AC:

97056

AN:

150320

AF XY:

0.642

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 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

African (AFR)

AF:

0.324

AC:

10391

AN:

32100

American (AMR)

AF:

0.780

AC:

27867

AN:

35740

Ashkenazi Jewish (ASJ)

AF:

0.585

AC:

14719

AN:

25166

East Asian (EAS)

AF:

0.763

AC:

27779

AN:

36402

South Asian (SAS)

AF:

0.598

AC:

47584

AN:

79528

European-Finnish (FIN)

AF:

0.658

AC:

27254

AN:

41398

Middle Eastern (MID)

AF:

0.589

AC:

3146

AN:

5342

European-Non Finnish (NFE)

AF:

0.629

AC:

679936

AN:

1080686

Other (OTH)

AF:

0.614

AC:

35668

AN:

58076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

18788

37575

56363

75150

93938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18302

36604

54906

73208

91510

<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:

0.559

AC:

84790

AN:

151750

Hom.:

25275

Cov.:

AF XY:

0.564

AC XY:

41835

AN XY:

74134

show subpopulations

African (AFR)

AF:

0.334

AC:

13821

AN:

41426

American (AMR)

AF:

0.704

AC:

10743

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.590

AC:

2046

AN:

3468

East Asian (EAS)

AF:

0.749

AC:

3840

AN:

5128

South Asian (SAS)

AF:

0.596

AC:

2872

AN:

4822

European-Finnish (FIN)

AF:

0.668

AC:

7019

AN:

10510

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.627

AC:

42527

AN:

67826

Other (OTH)

AF:

0.582

AC:

1231

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1829

3658

5486

7315

9144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<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:

0.601

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

May 31, 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

- -

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 18, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Jul 07, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

not specified

Benign:2

Dec 28, 2012

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

(source)

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;.;.;.;.;.

PhyloP100

0.21

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

PromoterAI

0.0011

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.075

gMVP

0.24

Mutation Taster

=88/12

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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