Variant rs754258809 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_207189.4(BRDT):c.2783G>A(p.Gly928Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000504 in 1,586,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

BRDT
NM_207189.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.69

Variant links:

Genes affected

BRDT (HGNC:1105): (bromodomain testis associated) BRDT is similar to the RING3 protein family. It possesses 2 bromodomain motifs and a PEST sequence (a cluster of proline, glutamic acid, serine, and threonine residues), characteristic of proteins that undergo rapid intracellular degradation. The bromodomain is found in proteins that regulate transcription. Several transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

BRDT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 1-92014213-G-A is Pathogenic according to our data. Variant chr1-92014213-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 437873.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-92014213-G-A is described in Lovd as [Pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.25335768). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRDT	NM_207189.4 linkuse as main transcript	c.2783G>A	p.Gly928Asp	missense_variant	19/19	ENST00000399546.7	NP_997072.2	Q58F21-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRDT	ENST00000399546.7 linkuse as main transcript	c.2783G>A	p.Gly928Asp	missense_variant	19/19	2	NM_207189.4	ENSP00000387822.3		Q58F21-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000418

AC:

AN:

1434534

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

713150

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000525

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.0000337

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152016

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Spermatogenic failure 21

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 28, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.;.;.;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.68

.;T;T;T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.25

T;T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.4

L;.;.;.;L

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-2.2

N;N;N;.;N

REVEL

Benign

0.19

Sift

Uncertain

0.0020

D;D;D;.;D

Sift4G

Uncertain

0.020

D;D;D;D;D

Polyphen

0.99

D;.;.;.;D

Vest4

0.24

MutPred

0.53

Gain of disorder (P = 0.0355);.;.;.;Gain of disorder (P = 0.0355);

MVP

0.65

MPC

0.46

ClinPred

0.78

GERP RS

4.3

Varity_R

0.44

gMVP

0.10

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