12-111672685-T-A

Variant names:

• chr12-111672685-T-A
• rs3782886
• NM_006768.5:c.723A>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R241K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRAP NM_006768.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006768.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRAP	NM_006768.5	MANE Select	c.723A>T	p.Arg241Ser	missense	Exon 5 of 12	NP_006759.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRAP	ENST00000419234.9	TSL:1 MANE Select	c.723A>T	p.Arg241Ser	missense	Exon 5 of 12	ENSP00000403524.3	Q7Z569-1
	BRAP	ENST00000327551.6	TSL:1	c.633A>T	p.Arg211Ser	missense	Exon 5 of 12	ENSP00000330813.5	J3KNN7
	BRAP	ENST00000871570.1		c.684A>T	p.Arg228Ser	missense	Exon 4 of 11	ENSP00000541629.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
PhyloP100		0.24
Varity_R		0.39
gMVP		0.63
Mutation Taster		=22/78	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3782886; hg19: chr12-112110489;