NM_017679.5:c.2543C>T

Variant names:

• chr17-61368444-C-T
• NM_017679.5:c.2543C>T

Variant summary

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

The NM_017679.5(BCAS3):​c.2543C>T​(p.Ala848Val) 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. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A848A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BCAS3 NM_017679.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.35
• 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]

TBX2-AS1 (HGNC:50355): (TBX2 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, 0.817

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.2543C>T	p.Ala848Val	missense	Exon 23 of 24	NP_060149.3
	BCAS3	NM_001353144.2		c.2678C>T	p.Ala893Val	missense	Exon 25 of 26	NP_001340073.1
	BCAS3	NM_001330413.2		c.2588C>T	p.Ala863Val	missense	Exon 24 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.2543C>T	p.Ala848Val	missense	Exon 23 of 24	ENSP00000385323.2	Q9H6U6-2
	BCAS3	ENST00000390652.9	TSL:1	c.2588C>T	p.Ala863Val	missense	Exon 24 of 25	ENSP00000375067.4	Q9H6U6-1
	BCAS3	ENST00000589222.5	TSL:1	c.2543C>T	p.Ala848Val	missense	Exon 23 of 26	ENSP00000466078.1	Q9H6U6-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459884 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725826

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110390

Other (OTH) AF: 0.00 AC: 0 AN: 60298

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	0.92
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.060	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	0.69	N
PhyloP100		7.3
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.19		Loss of helix (P = 0.3949)
MVP		0.75
MPC		1.2
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.73
gMVP		0.67

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

hg19: chr17-59445805; COSMIC: COSV104699278; COSMIC: COSV104699278;