17-61368344-G-A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting

The NM_017679.5(BCAS3):c.2443G>A(p.Val815Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000587 in 1,602,380 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 1 hom. )

Consequence

BCAS3
NM_017679.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.25

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:

ENSG00000267131 (HGNC:):

ENSG00000267131 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037422657).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000276 (42/152328) while in subpopulation AFR AF= 0.000914 (38/41584). AF 95% confidence interval is 0.000684. There are 0 homozygotes in gnomad4. There are 14 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 rank	MANE	Protein	UniProt
BCAS3	NM_017679.5 link	c.2443G>A	p.Val815Met	missense_variant	Exon 23 of 24	ENST00000407086.8	NP_060149.3	Q9H6U6-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAS3	ENST00000407086.8 link	c.2443G>A	p.Val815Met	missense_variant	Exon 23 of 24	1	NM_017679.5	ENSP00000385323.2		Q9H6U6-2

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000806

AC:

AN:

248068

Hom.:

AF XY:

0.0000520

AC XY:

AN XY:

134520

show subpopulations

Gnomad AFR exome

AF:

0.000840

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000359

AC:

AN:

1450052

Hom.:

Cov.:

AF XY:

0.0000306

AC XY:

AN XY:

719178

show subpopulations

Gnomad4 AFR exome

AF:

0.000571

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000508

Gnomad4 SAS exome

AF:

0.0000466

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000118

Gnomad4 OTH exome

AF:

0.000151

GnomAD4 genome

AF:

0.000276

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000914

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000619

Hom.:

Bravo

AF:

0.000351

ESP6500AA

AF:

0.00139

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000991

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Oct 20, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2488G>A (p.V830M) alteration is located in exon 24 (coding exon 23) of the BCAS3 gene. This alteration results from a G to A substitution at nucleotide position 2488, causing the valine (V) at amino acid position 830 to be replaced by a methionine (M). 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

Benign

0.14

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

.;.;T;.;.;T;.;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

D;D;D;D;D;D;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.037

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

.;.;N;N;.;.;.;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.46

.;N;N;.;N;.;.;.

REVEL

Benign

0.13

Sift

Benign

0.090

.;T;T;.;T;.;.;.

Sift4G

Benign

0.11

T;T;T;T;T;T;T;D

Polyphen

0.80

P;P;P;D;P;.;.;.

Vest4

0.43

MVP

0.16

MPC

0.65

ClinPred

0.042

GERP RS

5.9

Varity_R

0.095

gMVP

0.49

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

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