dbSNP rs1320244785: MED17:p.Gly3Glu (chr11-93784521-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004268.5(MED17):c.8G>A(p.Gly3Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,978 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G3V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MED17
NM_004268.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.02

Publications

0 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 links:

ENSG00000284057 (HGNC:):

ENSG00000284057 links:

TAF1D (HGNC:28759): (TATA-box binding protein associated factor, RNA polymerase I subunit D) TAF1D is a member of the SL1 complex, which includes TBP (MIM 600075) and TAF1A (MIM 604903), TAF1B (MIM 604904), and TAF1C (MIM 604905), and plays a role in RNA polymerase I transcription (Wang et al., 2004 [PubMed 15520167]; Gorski et al., 2007 [PubMed 17318177]).[supplied by OMIM, Jun 2009]

TAF1D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED17	NM_004268.5 link	c.8G>A	p.Gly3Glu	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.8G>A	p.Gly3Glu	missense_variant	Exon 1 of 12	1	NM_004268.5	ENSP00000251871.3		Q9NVC6-1
ENSG00000284057	ENST00000638767.1 link	c.676-107G>A		intron_variant	Intron 7 of 18	5		ENSP00000492220.1		A0A1W2PRB8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449978

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719210

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33260

American (AMR)

AF:

0.00

AC:

AN:

44424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26006

East Asian (EAS)

AF:

0.00

AC:

AN:

39362

South Asian (SAS)

AF:

0.00

AC:

AN:

86018

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50980

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1104404

Other (OTH)

AF:

0.00

AC:

AN:

59790

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.073

T;.;.;.;.;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

D;D;D;D;D;D

M_CAP

Benign

0.058

MetaRNN

Uncertain

0.59

D;D;D;D;D;D

MetaSVM

Benign

-0.51

MutationAssessor

Benign

1.7

L;.;.;.;.;.

PhyloP100

9.0

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.21

N;.;N;.;.;.

REVEL

Benign

0.28

Sift

Uncertain

0.028

D;.;D;.;.;.

Sift4G

Uncertain

0.052

T;.;D;.;.;.

Polyphen

0.29

B;.;.;.;.;.

Vest4

0.66

MutPred

0.54

Loss of MoRF binding (P = 0.0253);Loss of MoRF binding (P = 0.0253);Loss of MoRF binding (P = 0.0253);Loss of MoRF binding (P = 0.0253);Loss of MoRF binding (P = 0.0253);Loss of MoRF binding (P = 0.0253);

MVP

0.79

MPC

0.95

ClinPred

0.98

GERP RS

4.8

PromoterAI

-0.049

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.80

Mutation Taster

=53/47

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over