rs3782886

Variant names:

• chr12-111672685-T-A
• NM_006768.5:c.723A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-111672685-T-A
• chr12-111672685-T-C
• chr12-111672685-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006768.5(BRAP):​c.723A>T​(p.Arg241Ser) 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: BRAP NM_006768.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRAP	NM_006768.5	c.723A>T	p.Arg241Ser	missense_variant	Exon 5 of 12	ENST00000419234.9	NP_006759.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRAP	ENST00000419234.9	c.723A>T	p.Arg241Ser	missense_variant	Exon 5 of 12	1	NM_006768.5	ENSP00000403524.3
BRAP	ENST00000327551.6	c.633A>T	p.Arg211Ser	missense_variant	Exon 5 of 12	1		ENSP00000330813.5
BRAP	ENST00000547043.1	n.627A>T		non_coding_transcript_exon_variant	Exon 1 of 8	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.050	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.36	N;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.3	N;N
REVEL	Uncertain	0.43
Sift	Benign	0.23	T;T
Sift4G	Benign	0.27	T;T
Polyphen		1.0	D;.
Vest4		0.88
MutPred		0.56		Gain of catalytic residue at E240 (P = 0.0025);.;
MVP		0.56
MPC		0.95
ClinPred		0.94	D
GERP RS		3.6
Varity_R		0.39
gMVP		0.63

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: chr12-112110489;