17-61034748-A-G

Variant names:

• chr17-61034748-A-G
• rs139961894
• NM_017679.5:c.1720A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_017679.5(BCAS3):​c.1720A>G​(p.Arg574Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R574R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCAS3 NM_017679.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06
• Publications: 0 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.755

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.1720A>G	p.Arg574Gly	missense	Exon 17 of 24	NP_060149.3
	BCAS3	NM_001353144.2		c.1855A>G	p.Arg619Gly	missense	Exon 19 of 26	NP_001340073.1
	BCAS3	NM_001330413.2		c.1765A>G	p.Arg589Gly	missense	Exon 18 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.1720A>G	p.Arg574Gly	missense	Exon 17 of 24	ENSP00000385323.2	Q9H6U6-2
	BCAS3	ENST00000390652.9	TSL:1	c.1765A>G	p.Arg589Gly	missense	Exon 18 of 25	ENSP00000375067.4	Q9H6U6-1
	BCAS3	ENST00000589222.5	TSL:1	c.1720A>G	p.Arg574Gly	missense	Exon 17 of 26	ENSP00000466078.1	Q9H6U6-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.49
Sift	Benign	0.066	T
Sift4G	Uncertain	0.0070	D
Polyphen		0.98	D
Vest4		0.77
MutPred		0.52		Loss of loop (P = 9e-04)
MVP		0.92
MPC		1.3
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.59
gMVP		0.84

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

Other links and lift over

dbSNP: rs139961894; hg19: chr17-59112109;