Variant 1-91962764-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207189.4(BRDT):c.10C>T(p.Pro4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BRDT
NM_207189.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.913

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.118985385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRDT	NM_207189.4 linkuse as main transcript	c.10C>T	p.Pro4Ser	missense_variant	2/19	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.10C>T	p.Pro4Ser	missense_variant	2/19	2	NM_207189.4	ENSP00000387822.3		Q58F21-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1433312

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712166

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.10C>T (p.P4S) alteration is located in exon 2 (coding exon 1) of the BRDT gene. This alteration results from a C to T substitution at nucleotide position 10, causing the proline (P) at amino acid position 4 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.32

T;.;.;.;.;.;.;.;.;T;.;.;.;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.74

.;T;T;T;T;T;.;.;T;T;T;T;T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.12

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.28

N;N;N;.;.;.;.;.;.;.;.;.;.;N

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-4.8

D;D;D;D;D;D;D;D;D;D;D;D;D;D

REVEL

Benign

0.050

Sift

Benign

0.076

T;T;T;T;T;T;T;.;T;T;T;T;.;T

Sift4G

Benign

0.21

T;T;T;T;T;T;T;.;T;T;T;T;T;T

Polyphen

0.0070

B;.;.;.;.;.;.;.;.;.;.;.;.;B

Vest4

0.12

MVP

0.45

MPC

0.083

ClinPred

0.33

GERP RS

1.6

Varity_R

0.081

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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