17-61780993-A-T

Variant names:

• chr17-61780993-A-T
• NM_032043.3:c.1641T>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032043.3(BRIP1):​c.1641T>A​(p.Asp547Glu) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRIP1 NM_032043.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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]

ACMG classification

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, 0.783

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.1641T>A	p.Asp547Glu	missense_variant	Exon 12 of 20	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.1641T>A	p.Asp547Glu	missense_variant	Exon 12 of 20	1	NM_032043.3	ENSP00000259008.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.42	T;.
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Uncertain	0.29	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Uncertain	-0.018	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.8	D;.
REVEL	Uncertain	0.54
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	D;.
Vest4		0.69
MutPred		0.35		Loss of ubiquitination at K549 (P = 0.0896);Loss of ubiquitination at K549 (P = 0.0896);
MVP		0.89
MPC		0.66
ClinPred		0.99	D
GERP RS		1.7
Varity_R		0.75
gMVP		0.69

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: chr17-59858354;