Variant 19-39397750-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001317770.3(MED29):c.584G>C(p.Arg195Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,583,642 control chromosomes in the GnomAD database, including 11,589 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/10 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1111 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10478 hom. )

Consequence

MED29
NM_001317770.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.02

Variant links:

Genes affected

MED29 (HGNC:23074): (mediator complex subunit 29) MED29 is a subunit of the Mediator complex, a multiprotein coactivator of RNA transcription that interacts with DNA-bound transcriptional activators, RNA polymerase II (see MIM 180660), and general initiation factors (Sato et al., 2003 [PubMed 14576168]).[supplied by OMIM, Aug 2009]

MED29 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016457736).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED29	NM_017592.4 link	c.*51G>C		3_prime_UTR_variant	4/4	ENST00000315588.11	NP_060062.2	Q9NX70-1B4DUA7
MED29	NM_001317770.3 link	c.584G>C	p.Arg195Thr	missense_variant	4/4		NP_001304699.2	Q9NX70-2
MED29	NR_133915.3 link	n.640G>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED29	ENST00000315588.11 link	c.*51G>C		3_prime_UTR_variant	4/4	1	NM_017592.4	ENSP00000314343.5		Q9NX70-1

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16797

AN:

152136

Hom.:

1106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0929

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.209

Gnomad ASJ

AF:

0.0571

Gnomad EAS

AF:

0.0938

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.0694

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.113

GnomAD3 exomes

AF:

0.133

AC:

29748

AN:

223090

Hom.:

2562

AF XY:

0.131

AC XY:

15914

AN XY:

121674

show subpopulations

Gnomad AFR exome

AF:

0.0957

Gnomad AMR exome

AF:

0.273

Gnomad ASJ exome

AF:

0.0548

Gnomad EAS exome

AF:

0.0902

Gnomad SAS exome

AF:

0.202

Gnomad FIN exome

AF:

0.0654

Gnomad NFE exome

AF:

0.0972

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.114

AC:

162490

AN:

1431388

Hom.:

10478

Cov.:

AF XY:

0.115

AC XY:

81645

AN XY:

709912

show subpopulations

Gnomad4 AFR exome

AF:

0.0900

Gnomad4 AMR exome

AF:

0.264

Gnomad4 ASJ exome

AF:

0.0540

Gnomad4 EAS exome

AF:

0.0786

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.0681

Gnomad4 NFE exome

AF:

0.106

Gnomad4 OTH exome

AF:

0.118

GnomAD4 genome

AF:

0.110

AC:

16812

AN:

152254

Hom.:

1111

Cov.:

AF XY:

0.112

AC XY:

8364

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0928

Gnomad4 AMR

AF:

0.209

Gnomad4 ASJ

AF:

0.0571

Gnomad4 EAS

AF:

0.0927

Gnomad4 SAS

AF:

0.199

Gnomad4 FIN

AF:

0.0694

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.117

Alfa

AF:

0.0585

Hom.:

Bravo

AF:

0.121

TwinsUK

AF:

0.108

AC:

402

ALSPAC

AF:

0.115

AC:

445

ESP6500AA

AF:

0.0893

AC:

393

ESP6500EA

AF:

0.102

AC:

879

ExAC

AF:

0.119

AC:

14432

Asia WGS

AF:

0.182

AC:

633

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

9.9

DANN

Benign

0.75

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0016

PrimateAI

Benign

0.30

Vest4

0.18

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over