12-111679218-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_006768.5(BRAP):āc.566A>Gā(p.Glu189Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,609,958 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 30)
Exomes š: 0.000017 ( 1 hom. )
Consequence
BRAP
NM_006768.5 missense
NM_006768.5 missense
Scores
3
12
4
Clinical Significance
Conservation
PhyloP100: 7.60
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 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, 0.819
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRAP | NM_006768.5 | c.566A>G | p.Glu189Gly | missense_variant | 4/12 | ENST00000419234.9 | |
BRAP | XM_005253944.5 | c.689A>G | p.Glu230Gly | missense_variant | 4/12 | ||
BRAP | XM_017019992.2 | c.404A>G | p.Glu135Gly | missense_variant | 3/11 | ||
BRAP | XM_047429622.1 | c.119A>G | p.Glu40Gly | missense_variant | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAP | ENST00000419234.9 | c.566A>G | p.Glu189Gly | missense_variant | 4/12 | 1 | NM_006768.5 | P1 | |
BRAP | ENST00000327551.6 | c.476A>G | p.Glu159Gly | missense_variant | 4/12 | 1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249854Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135094
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1457770Hom.: 1 Cov.: 30 AF XY: 0.0000152 AC XY: 11AN XY: 724970
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74346
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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 24, 2023 | The c.566A>G (p.E189G) alteration is located in exon 4 (coding exon 4) of the BRAP gene. This alteration results from a A to G substitution at nucleotide position 566, causing the glutamic acid (E) at amino acid position 189 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
T;D
Polyphen
P;.
Vest4
MutPred
Gain of catalytic residue at V187 (P = 0);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at