Variant chr8-117520949-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_080651.4(MED30):c.73G>T(p.Ala25Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00225 in 1,612,398 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 37 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 41 hom. )

Consequence

MED30
NM_080651.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.11

Variant links:

Genes affected

MED30 (HGNC:23032): (mediator complex subunit 30) The multiprotein TRAP/Mediator complex facilitates gene expression through a wide variety of transcriptional activators. MED30 is a component of this complex that appears to be metazoan specific (Baek et al., 2002 [PubMed 11909976]).[supplied by OMIM, Nov 2010]

MED30 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040160716).

BP6

Variant 8-117520949-G-T is Benign according to our data. Variant chr8-117520949-G-T is described in ClinVar as [Benign]. Clinvar id is 776380.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.012 (1822/152328) while in subpopulation AFR AF= 0.0414 (1722/41566). AF 95% confidence interval is 0.0398. There are 37 homozygotes in gnomad4. There are 868 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MED30	NM_080651.4 linkuse as main transcript	c.73G>T	p.Ala25Ser	missense_variant	1/4	ENST00000297347.7
MED30	NM_001363182.2 linkuse as main transcript	c.73G>T	p.Ala25Ser	missense_variant	1/4
MED30	NM_001282986.2 linkuse as main transcript	c.73G>T	p.Ala25Ser	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED30	ENST00000297347.7 linkuse as main transcript	c.73G>T	p.Ala25Ser	missense_variant	1/4	1	NM_080651.4	P1	Q96HR3-1
MED30	ENST00000522839.1 linkuse as main transcript	c.73G>T	p.Ala25Ser	missense_variant	1/3	1			Q96HR3-2
MED30	ENST00000519879.1 linkuse as main transcript	n.186G>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1820

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0415

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00318

AC:

773

AN:

243110

Hom.:

AF XY:

0.00243

AC XY:

323

AN XY:

132822

show subpopulations

Gnomad AFR exome

AF:

0.0452

Gnomad AMR exome

AF:

0.00215

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000371

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.00123

AC:

1801

AN:

1460070

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

770

AN XY:

726218

show subpopulations

Gnomad4 AFR exome

AF:

0.0449

Gnomad4 AMR exome

AF:

0.00240

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

AF:

0.0120

AC:

1822

AN:

152328

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

868

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0414

Gnomad4 AMR

AF:

0.00470

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.00513

Hom.:

Bravo

AF:

0.0137

ESP6500AA

AF:

0.0375

AC:

165

ESP6500EA

AF:

0.000350

AC:

ExAC

AF:

0.00367

AC:

445

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.044

T;.

Eigen

Benign

-0.086

Eigen_PC

Benign

0.047

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.70

T;T

MetaRNN

Benign

0.0040

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.92

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.44

N;N

REVEL

Benign

0.26

Sift

Benign

0.43

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.61

P;.

Vest4

0.13

MVP

0.26

MPC

0.48

ClinPred

0.060

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.096

gMVP

0.42

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