17-61040857-A-G

Variant names:

• chr17-61040857-A-G
• NM_017679.5:c.1994A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017679.5(BCAS3):​c.1994A>G​(p.Asp665Gly) 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 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: 8.95

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4165363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAS3	NM_017679.5	c.1994A>G	p.Asp665Gly	missense_variant	Exon 19 of 24	ENST00000407086.8	NP_060149.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAS3	ENST00000407086.8	c.1994A>G	p.Asp665Gly	missense_variant	Exon 19 of 24	1	NM_017679.5	ENSP00000385323.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Nov 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2039A>G (p.D680G) alteration is located in exon 20 (coding exon 19) of the BCAS3 gene. This alteration results from a A to G substitution at nucleotide position 2039, causing the aspartic acid (D) at amino acid position 680 to be replaced by a glycine (G). 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	0.54
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	.;.;T;.;.;T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D;D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.42	T;T;T;T;T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.9	.;.;L;L;.;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.6	.;D;D;.;D;.;.
REVEL	Benign	0.19
Sift	Benign	0.14	.;T;T;.;T;.;.
Sift4G	Uncertain	0.023	D;D;D;D;D;D;D
Polyphen		1.0	D;D;D;B;D;.;.
Vest4		0.59
MutPred		0.53		.;.;Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);.;.;.;
MVP		0.45
MPC		1.4
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.48
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr17-59118218;