17-60868682-C-T

Variant names:

• chr17-60868682-C-T
• rs377752373
• NM_017679.5:c.583C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_017679.5(BCAS3):​c.583C>T​(p.Arg195Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000814 in 1,560,608 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000080 (0 hom.)
• Consequence: BCAS3 NM_017679.5 missense, splice_region
• Scores: Splicing: ADA: 0.0001152
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09
• Publications: 4 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 Gene-Disease associations (from GenCC):

• Hengel-Maroofian-Schols syndrome

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0000986 (15/152128) while in subpopulation AFR AF = 0.000217 (9/41496). AF 95% confidence interval is 0.000113. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.583C>T	p.Arg195Trp	missense splice_region	Exon 8 of 24	NP_060149.3
	BCAS3	NM_001353144.2		c.583C>T	p.Arg195Trp	missense splice_region	Exon 8 of 26	NP_001340073.1
	BCAS3	NM_001330413.2		c.583C>T	p.Arg195Trp	missense splice_region	Exon 8 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.583C>T	p.Arg195Trp	missense splice_region	Exon 8 of 24	ENSP00000385323.2	Q9H6U6-2
	BCAS3	ENST00000390652.9	TSL:1	c.583C>T	p.Arg195Trp	missense splice_region	Exon 8 of 25	ENSP00000375067.4	Q9H6U6-1
	BCAS3	ENST00000589222.5	TSL:1	c.583C>T	p.Arg195Trp	missense splice_region	Exon 8 of 26	ENSP00000466078.1	Q9H6U6-7

Frequencies

GnomAD3 genomes AF: 0.0000987 AC: 15 AN: 152012 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000420 AC: 9 AN: 214186 AF XY: 0.0000256

Gnomad AFR exome AF: 0.0000744

Gnomad AMR exome AF: 0.0000396

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000680

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000489

Gnomad OTH exome AF: 0.000203

GnomAD4 exome AF: 0.0000795 AC: 112 AN: 1408480 Hom.: 0 Cov.: 24 AF XY: 0.0000827 AC XY: 58 AN XY: 701476

African (AFR) AF: 0.0000661 AC: 2 AN: 30262

American (AMR) AF: 0.00 AC: 0 AN: 36300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24826

East Asian (EAS) AF: 0.00 AC: 0 AN: 37522

South Asian (SAS) AF: 0.0000755 AC: 6 AN: 79490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 0.0000932 AC: 101 AN: 1083364

Other (OTH) AF: 0.0000515 AC: 3 AN: 58210

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74386

African (AFR) AF: 0.000217 AC: 9 AN: 41496

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000395 Hom.: 0

Bravo AF: 0.0000831

ESP6500AA AF: 0.000275 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000414 AC: 5

Asia WGS AF: 0.000866 AC: 3 AN: 3478

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	Uncertain	0.35
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	0.044
Eigen_PC	Benign	-0.036
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.1
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.22
Sift	Benign	0.050	D
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.70
MVP		0.35
MPC		1.1
ClinPred		0.92	D
GERP RS		-0.32
Varity_R		0.27
gMVP		0.61
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.084
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: rs377752373; hg19: chr17-58946043; COSMIC: COSV66771042;