rs756787438

Variant summary

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

The NM_006768.5(BRAP):​c.1693G>T​(p.Ala565Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A565T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

BRAP
NM_006768.5 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.730
Variant links:
Genes affected
BRAP (HGNC:1099): (BRCA1 associated protein) The protein encoded by this gene was identified by its ability to bind to the nuclear localization signal of BRCA1 and other proteins. It is a cytoplasmic protein which may regulate nuclear targeting by retaining proteins with a nuclear localization signal in the cytoplasm. [provided by RefSeq, Jul 2008]

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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=0.06644294).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRAPNM_006768.5 linkc.1693G>T p.Ala565Ser missense_variant Exon 12 of 12 ENST00000419234.9 NP_006759.3 Q7Z569-1Q59H81

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRAPENST00000419234.9 linkc.1693G>T p.Ala565Ser missense_variant Exon 12 of 12 1 NM_006768.5 ENSP00000403524.3 Q7Z569-1
BRAPENST00000327551.6 linkc.1603G>T p.Ala535Ser missense_variant Exon 12 of 12 1 ENSP00000330813.5 J3KNN7
BRAPENST00000547043.1 linkn.*54G>T downstream_gene_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251412
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461846
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727228
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:
0.00000719
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000492
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.0000247
AC:
3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
8.9
DANN
Benign
0.97
DEOGEN2
Benign
0.33
T;T
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.80
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.85
D;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.066
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.7
L;.
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-0.56
N;N
REVEL
Benign
0.078
Sift
Benign
0.23
T;T
Sift4G
Benign
0.21
T;T
Polyphen
0.37
B;.
Vest4
0.075
MVP
0.36
MPC
0.13
ClinPred
0.14
T
GERP RS
-1.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.040
gMVP
0.32

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: rs756787438; hg19: chr12-112082089; API