17-60689735-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017679.5(BCAS3):c.188T>C(p.Val63Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 5.34

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24985853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCAS3	NM_017679.5	c.188T>C	p.Val63Ala	missense_variant	4/24	ENST00000407086.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCAS3	ENST00000407086.8	c.188T>C	p.Val63Ala	missense_variant	4/24	1	NM_017679.5	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

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

Dec 14, 2021

The c.188T>C (p.V63A) alteration is located in exon 4 (coding exon 3) of the BCAS3 gene. This alteration results from a T to C substitution at nucleotide position 188, causing the valine (V) at amino acid position 63 to be replaced by an alanine (A). 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	Pathogenic	0.57
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
Cadd	Uncertain	24
Dann	Benign	0.56
DEOGEN2	Benign	0.033	T;.;.;T;.;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.040
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D;D;D;D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.25	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.77	T
Sift4G	Pathogenic	0.0	D;T;T;T;T;T
Polyphen		0.20, 0.38, 0.064	.;B;B;B;.;.
Vest4		0.78, 0.78, 0.78, 0.76, 0.78
MutPred		0.41		Loss of stability (P = 0.0397);Loss of stability (P = 0.0397);Loss of stability (P = 0.0397);Loss of stability (P = 0.0397);Loss of stability (P = 0.0397);Loss of stability (P = 0.0397);
MVP		0.49
MPC		0.48
ClinPred		0.81	D
GERP RS		5.1
Varity_R		0.13
gMVP		0.55

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: chr17-58767096;