NM_032043.3:c.2325T>A

Variant names:

• chr17-61743067-A-T
• NM_032043.3:c.2325T>A

Variant summary

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

The NM_032043.3(BRIP1):​c.2325T>A​(p.Asn775Lys) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N775S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRIP1 NM_032043.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.410

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, 0.826

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.2325T>A	p.Asn775Lys	missense_variant	Exon 16 of 20	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.2325T>A	p.Asn775Lys	missense_variant	Exon 16 of 20	1	NM_032043.3	ENSP00000259008.2

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	Uncertain	0.54
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Benign	0.86
DEOGEN2	Uncertain	0.69	D;.
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-4.5	D;.
REVEL	Uncertain	0.43
Sift	Benign	0.055	T;.
Sift4G	Uncertain	0.014	D;T
Polyphen		1.0	D;.
Vest4		0.90
MutPred		0.50		Gain of ubiquitination at N775 (P = 0.0203);Gain of ubiquitination at N775 (P = 0.0203);
MVP		0.78
MPC		0.72
ClinPred		0.97	D
GERP RS		1.6
Varity_R		0.55
gMVP		0.79

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: chr17-59820428;