17-61078367-G-C

Variant names:

• chr17-61078367-G-C
• rs781695048
• NM_017679.5:c.2165G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_017679.5(BCAS3):​c.2165G>C​(p.Arg722Pro) variant causes a missense change involving the alteration of a 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. R722C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCAS3 NM_017679.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.72
• Publications: 1 publications found

Genes affected

BCAS3 (HGNC:14347): (BCAS3 microtubule associated cell migration factor) Enables several functions, including acetyltransferase activator activity; beta-tubulin binding activity; and histone acetyltransferase binding activity. Involved in cellular response to estrogen stimulus; positive regulation of catalytic activity; and positive regulation of transcription by RNA polymerase II. Located in nucleus; phagophore assembly site; and transcriptionally active chromatin. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

BCAS3-AS1 (HGNC:56376): (BCAS3 antisense RNA 1)

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, 0.857

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017679.5. 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
	BCAS3	NM_017679.5	MANE Select	c.2165G>C	p.Arg722Pro	missense	Exon 21 of 24	NP_060149.3
	BCAS3	NM_001353144.2		c.2300G>C	p.Arg767Pro	missense	Exon 23 of 26	NP_001340073.1
	BCAS3	NM_001330413.2		c.2210G>C	p.Arg737Pro	missense	Exon 22 of 26	NP_001317342.1	Q9H6U6-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAS3	ENST00000407086.8	TSL:1 MANE Select	c.2165G>C	p.Arg722Pro	missense	Exon 21 of 24	ENSP00000385323.2	Q9H6U6-2
	BCAS3	ENST00000390652.9	TSL:1	c.2210G>C	p.Arg737Pro	missense	Exon 22 of 25	ENSP00000375067.4	Q9H6U6-1
	BCAS3	ENST00000589222.5	TSL:1	c.2165G>C	p.Arg722Pro	missense	Exon 21 of 26	ENSP00000466078.1	Q9H6U6-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
PhyloP100		9.7
PromoterAI		0.0015	Neutral
Varity_R		0.95
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs781695048; hg19: chr17-59155728;