NM_017679.5:c.2182C>T

Variant names:

• chr17-61078384-C-T
• rs2143487816
• NM_017679.5:c.2182C>T

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_017679.5(BCAS3):​c.2182C>T​(p.Gln728*) variant causes a stop gained 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 Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCAS3 NM_017679.5 stop_gained
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.69
• Publications: 1 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: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-61078384-C-T is Pathogenic according to our data. Variant chr17-61078384-C-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 993272.Status of the report is no_assertion_criteria_provided, 0 stars.

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.2182C>T	p.Gln728*	stop_gained	Exon 21 of 24	NP_060149.3
	BCAS3	NM_001353144.2		c.2317C>T	p.Gln773*	stop_gained	Exon 23 of 26	NP_001340073.1
	BCAS3	NM_001330413.2		c.2227C>T	p.Gln743*	stop_gained	Exon 22 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.2182C>T	p.Gln728*	stop_gained	Exon 21 of 24	ENSP00000385323.2	Q9H6U6-2
	BCAS3	ENST00000390652.9	TSL:1	c.2227C>T	p.Gln743*	stop_gained	Exon 22 of 25	ENSP00000375067.4	Q9H6U6-1
	BCAS3	ENST00000589222.5	TSL:1	c.2182C>T	p.Gln728*	stop_gained	Exon 21 of 26	ENSP00000466078.1	Q9H6U6-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Global developmental delay (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.66
CADD	Pathogenic	39
DANN	Uncertain	1.0
Eigen	Pathogenic	1.2
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		7.7
Vest4		0.56
GERP RS		5.6
PromoterAI		-0.0078	Neutral

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: rs2143487816; hg19: chr17-59155745;