17-60868682-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS1_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

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

Hengel-Maroofian-Schols syndrome
Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

BCAS3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 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. 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.583C>T	p.Arg195Trp	missense_variant, splice_region_variant	Exon 8 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.583C>T	p.Arg195Trp	missense_variant, splice_region_variant	Exon 8 of 24	1	NM_017679.5	ENSP00000385323.2		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

GnomAD2 exomes

AF:

0.0000420

AC:

AN:

214186

AF XY:

0.0000256

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 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

African (AFR)

AF:

0.0000661

AC:

AN:

30262

American (AMR)

AF:

0.00

AC:

AN:

36300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24826

East Asian (EAS)

AF:

0.00

AC:

AN:

37522

South Asian (SAS)

AF:

0.0000755

AC:

AN:

79490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52898

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5608

European-Non Finnish (NFE)

AF:

0.0000932

AC:

101

AN:

1083364

Other (OTH)

AF:

0.0000515

AC:

AN:

58210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41496

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000395

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

May 18, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

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

PhyloP100

1.1

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

Mutation Taster

=71/29

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

17-60868682-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over