Variant 17-60868682-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting

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

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCAS3	NM_017679.5 linkuse as main transcript	c.583C>T	p.Arg195Trp	missense_variant, splice_region_variant	8/24	ENST00000407086.8	NP_060149.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCAS3	ENST00000407086.8 linkuse as main transcript	c.583C>T	p.Arg195Trp	missense_variant, splice_region_variant	8/24	1	NM_017679.5	ENSP00000385323	P3	Q9H6U6-2

Frequencies

GnomAD3 genomes

AF:

0.0000987

AC:

AN:

152012

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0000420

AC:

AN:

214186

Hom.:

AF XY:

0.0000256

AC XY:

AN XY:

117090

show subpopulations

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 SAS exome

AF:

0.00

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.:

Cov.:

AF XY:

0.0000827

AC XY:

AN XY:

701476

show subpopulations

Gnomad4 AFR exome

AF:

0.0000661

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000755

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000932

Gnomad4 OTH exome

AF:

0.0000515

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000326

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.000275

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000414

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 18, 2022

The c.583C>T (p.R195W) alteration is located in exon 8 (coding exon 7) of the BCAS3 gene. This alteration results from a C to T substitution at nucleotide position 583, causing the arginine (R) at amino acid position 195 to be replaced by a tryptophan (W). 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

0.35

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

.;.;T;.;.

Eigen

Benign

0.044

Eigen_PC

Benign

-0.036

FATHMM_MKL

Uncertain

0.83

LIST_S2

Pathogenic

0.99

D;D;D;D;D

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.55

D;D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;M;M;M;M

MutationTaster

Benign

0.53

D;D;D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-4.7

.;D;D;.;D

REVEL

Benign

0.22

Sift

Benign

0.050

.;D;D;.;D

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

1.0

D;D;D;.;.

Vest4

0.70

MVP

0.35

MPC

1.1

ClinPred

0.92

GERP RS

-0.32

Varity_R

0.27

gMVP

0.61

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over