Variant 1-91979599-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_207189.4(BRDT):c.1129C>A(p.Pro377Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P377R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

BRDT
NM_207189.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.73

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:

BRDT (HGNC:):

BRDT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.767

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRDT	NM_207189.4 linkuse as main transcript	c.1129C>A	p.Pro377Thr	missense_variant	8/19	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.1129C>A	p.Pro377Thr	missense_variant	8/19	2	NM_207189.4	ENSP00000387822.3		Q58F21-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723988

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 22, 2023

The c.1141C>A (p.P381T) alteration is located in exon 8 (coding exon 7) of the BRDT gene. This alteration results from a C to A substitution at nucleotide position 1141, causing the proline (P) at amino acid position 381 to be replaced by a threonine (T). 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

0.15

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

D;.;.;.;T;D

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

.;D;D;D;D;D

M_CAP

Benign

0.030

MetaRNN

Pathogenic

0.77

D;D;D;D;D;D

MetaSVM

Benign

-0.67

MutationAssessor

Pathogenic

3.6

H;.;.;.;.;H

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-7.3

D;D;D;.;D;D

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

D;D;D;.;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

1.0

D;.;.;.;.;D

Vest4

0.55

MutPred

0.47

Gain of glycosylation at P377 (P = 0.0372);.;.;.;Gain of glycosylation at P377 (P = 0.0372);Gain of glycosylation at P377 (P = 0.0372);

MVP

0.78

MPC

0.45

ClinPred

1.0

GERP RS

5.7

Varity_R

0.79

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over