17-60747235-A-C

Position:

• chr17-60747235-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017679.5(BCAS3):​c.359A>C​(p.His120Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCAS3 NM_017679.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.52

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCAS3	NM_017679.5	c.359A>C	p.His120Pro	missense_variant	6/24	ENST00000407086.8	NP_060149.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCAS3	ENST00000407086.8	c.359A>C	p.His120Pro	missense_variant	6/24	1	NM_017679.5	ENSP00000385323	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.359A>C (p.H120P) alteration is located in exon 6 (coding exon 5) of the BCAS3 gene. This alteration results from a A to C substitution at nucleotide position 359, causing the histidine (H) at amino acid position 120 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T;.;.;T;.;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.45	T;T;T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	.;M;M;M;M;M
MutationTaster	Benign	0.86	D;D;D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-4.3	.;.;D;D;.;D
REVEL	Benign	0.23
Sift	Uncertain	0.012	.;.;D;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		0.98, 0.95, 0.92	.;D;P;P;.;.
Vest4		0.55, 0.54, 0.54, 0.53, 0.56
MutPred		0.51		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP		0.43
MPC		1.1
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.54
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs764109288; hg19: chr17-58824596;