rs34380494

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004268.5(MED17):c.1482A>G(p.Gln494Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,601,822 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 33 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 32 hom. )

Consequence

MED17
NM_004268.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.85

Publications

2 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 11-93807533-A-G is Benign according to our data. Variant chr11-93807533-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 129595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.85 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0111 (1695/152316) while in subpopulation AFR AF = 0.0378 (1570/41564). AF 95% confidence interval is 0.0362. There are 33 homozygotes in GnomAd4. There are 811 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 33 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004268.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED17	NM_004268.5	MANE Select	c.1482A>G	p.Gln494Gln	synonymous	Exon 10 of 12	NP_004259.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MED17	ENST00000251871.9	TSL:1 MANE Select	c.1482A>G	p.Gln494Gln	synonymous	Exon 10 of 12	ENSP00000251871.3
ENSG00000284057	ENST00000638767.1	TSL:5	c.2043A>G	p.Gln681Gln	synonymous	Exon 17 of 19	ENSP00000492220.1
MED17	ENST00000529626.2	TSL:1	n.1485A>G		non_coding_transcript_exon	Exon 6 of 8

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1687

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0377

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00536

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.00305

AC:

767

AN:

251370

AF XY:

0.00248

show subpopulations

Gnomad AFR exome

AF:

0.0385

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.00117

AC:

1689

AN:

1449506

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

828

AN XY:

722030

show subpopulations

African (AFR)

AF:

0.0358

AC:

1185

AN:

33144

American (AMR)

AF:

0.00201

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26042

East Asian (EAS)

AF:

0.0000758

AC:

AN:

39586

South Asian (SAS)

AF:

0.00238

AC:

205

AN:

86006

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00226

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0000554

AC:

AN:

1100886

Other (OTH)

AF:

0.00217

AC:

130

AN:

59984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

152

229

305

381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.0111

AC:

1695

AN:

152316

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

811

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0378

AC:

1570

AN:

41564

American (AMR)

AF:

0.00536

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00228

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68034

Other (OTH)

AF:

0.0123

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

168

253

337

421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00378

Hom.:

Bravo

AF:

0.0123

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.9

(source)

DANN

Benign

0.59

PhyloP100

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over