dbSNP rs10747493: BRDT:p.Pro696Gln (chr1-91992286-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207189.4(BRDT):c.2087C>A(p.Pro696Gln) 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. 16/22 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: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BRDT
NM_207189.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.926

Publications

27 publications found

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 Gene-Disease associations (from GenCC):

spermatogenic failure 21
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

BRDT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05376783).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207189.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BRDT	NM_207189.4	MANE Select	c.2087C>A	p.Pro696Gln	missense	Exon 14 of 19	NP_997072.2
BRDT	NM_001242806.2		c.2099C>A	p.Pro700Gln	missense	Exon 14 of 19	NP_001229735.2
BRDT	NM_001242805.2		c.2087C>A	p.Pro696Gln	missense	Exon 15 of 20	NP_001229734.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BRDT	ENST00000399546.7	TSL:2 MANE Select	c.2087C>A	p.Pro696Gln	missense	Exon 14 of 19	ENSP00000387822.3
BRDT	ENST00000362005.7	TSL:1	c.2087C>A	p.Pro696Gln	missense	Exon 15 of 20	ENSP00000354568.3
BRDT	ENST00000402388.1	TSL:1	c.2087C>A	p.Pro696Gln	missense	Exon 14 of 19	ENSP00000384051.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1354248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

673684

African (AFR)

AF:

0.00

AC:

AN:

28692

American (AMR)

AF:

0.00

AC:

AN:

29292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24052

East Asian (EAS)

AF:

0.00

AC:

AN:

36252

South Asian (SAS)

AF:

0.00

AC:

AN:

69752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52510

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5514

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1051860

Other (OTH)

AF:

0.00

AC:

AN:

56324

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

232133

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.29

(source)

DANN

Benign

0.11

DEOGEN2

Benign

0.067

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.18

M_CAP

Benign

0.0019

MetaRNN

Benign

0.054

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.34

PhyloP100

-0.93

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.42

REVEL

Benign

0.014

Sift

Benign

0.14

Sift4G

Benign

0.19

Polyphen

0.0

Vest4

0.078

MutPred

0.17

Loss of helix (P = 0.0123)

MVP

0.30

MPC

0.074

ClinPred

0.047

GERP RS

0.031

Varity_R

0.025

gMVP

0.11

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over