1-91976314-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207189.4(BRDT):​c.494C>A​(p.Pro165His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,611,244 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

BRDT
NM_207189.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.337
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05931714).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRDTNM_207189.4 linkc.494C>A p.Pro165His missense_variant Exon 5 of 19 ENST00000399546.7 NP_997072.2 Q58F21-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRDTENST00000399546.7 linkc.494C>A p.Pro165His missense_variant Exon 5 of 19 2 NM_207189.4 ENSP00000387822.3 Q58F21-1

Frequencies

GnomAD3 genomes
AF:
0.000164
AC:
25
AN:
152076
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000604
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
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
GnomAD3 exomes
AF:
0.0000402
AC:
10
AN:
248482
Hom.:
0
AF XY:
0.0000298
AC XY:
4
AN XY:
134406
show subpopulations
Gnomad AFR exome
AF:
0.000623
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1459168
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
725888
show subpopulations
Gnomad4 AFR exome
AF:
0.000601
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
AF:
0.000164
AC:
25
AN:
152076
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74252
show subpopulations
Gnomad4 AFR
AF:
0.000604
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000323
Hom.:
0
Bravo
AF:
0.000155
ESP6500AA
AF:
0.00136
AC:
6
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000741
AC:
9

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.506C>A (p.P169H) alteration is located in exon 5 (coding exon 4) of the BRDT gene. This alteration results from a C to A substitution at nucleotide position 506, causing the proline (P) at amino acid position 169 to be replaced by a histidine (H). 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
0.094
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.48
T;.;.;.;.;.;T;T
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.55
FATHMM_MKL
Benign
0.030
N
LIST_S2
Benign
0.66
.;T;T;T;T;T;T;T
M_CAP
Benign
0.0038
T
MetaRNN
Benign
0.059
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.8
M;.;.;.;.;.;.;M
PrimateAI
Benign
0.28
T
PROVEAN
Uncertain
-3.8
D;D;D;.;D;D;D;D
REVEL
Benign
0.021
Sift
Uncertain
0.022
D;D;D;.;D;D;T;D
Sift4G
Benign
0.070
T;T;T;T;D;D;D;T
Polyphen
0.97
D;.;.;.;.;.;.;D
Vest4
0.22
MVP
0.56
MPC
0.16
ClinPred
0.18
T
GERP RS
2.1
Varity_R
0.14
gMVP
0.21

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.

Other links and lift over

dbSNP: rs373881759; hg19: chr1-92441871; API