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GeneBe

rs138743097

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_032043.3(BRIP1):c.778A>T(p.Thr260Ser) 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. 13/21 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. T260A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

BRIP1
NM_032043.3 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.50
Variant links:
Genes affected
BRIP1 (HGNC:20473): (BRCA1 interacting helicase 1) The protein encoded by this gene is a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer, type 1 (BRCA1). The bound complex is important in the normal double-strand break repair function of breast cancer, type 1 (BRCA1). This gene may be a target of germline cancer-inducing mutations. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 17 uncertain in NM_032043.3
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32521346).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BRIP1NM_032043.3 linkuse as main transcriptc.778A>T p.Thr260Ser missense_variant 7/20 ENST00000259008.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BRIP1ENST00000259008.7 linkuse as main transcriptc.778A>T p.Thr260Ser missense_variant 7/201 NM_032043.3 P2Q9BX63-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.089
T
BayesDel_noAF
Benign
-0.37
Cadd
Benign
20
Dann
Uncertain
0.99
DEOGEN2
Uncertain
0.42
T;.
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.77
T;T
M_CAP
Benign
0.047
D
MetaRNN
Benign
0.33
T;T
MetaSVM
Uncertain
-0.27
T
MutationAssessor
Benign
1.0
L;L
MutationTaster
Benign
0.59
D;D
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-1.9
N;.
REVEL
Benign
0.23
Sift
Benign
0.11
T;.
Sift4G
Benign
0.13
T;T
Polyphen
0.89
P;.
Vest4
0.50
MutPred
0.57
Loss of phosphorylation at T260 (P = 0.0718);Loss of phosphorylation at T260 (P = 0.0718);
MVP
0.76
MPC
0.21
ClinPred
0.70
D
GERP RS
5.3
Varity_R
0.26
gMVP
0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-59885968; API