Genetic Variant BCAS3:p.Ile60Val (chr17-60689725-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_017679.5(BCAS3):c.178A>G(p.Ile60Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BCAS3
NM_017679.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17

Publications

0 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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30238628).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAS3	NM_017679.5 link	c.178A>G	p.Ile60Val	missense_variant	Exon 4 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.178A>G	p.Ile60Val	missense_variant	Exon 4 of 24	1	NM_017679.5	ENSP00000385323.2		Q9H6U6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249118

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457148

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33370

American (AMR)

AF:

0.00

AC:

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39586

South Asian (SAS)

AF:

0.00

AC:

AN:

86028

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1108056

Other (OTH)

AF:

0.00

AC:

AN:

60222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Mar 08, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.178A>G (p.I60V) alteration is located in exon 4 (coding exon 3) of the BCAS3 gene. This alteration results from a A to G substitution at nucleotide position 178, causing the isoleucine (I) at amino acid position 60 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

T;.;.;T;.;.

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D;D;D;D;D

M_CAP

Benign

0.0090

MetaRNN

Benign

0.30

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

.;L;L;L;L;L

PhyloP100

6.2

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.91

.;.;N;N;.;N

REVEL

Benign

0.19

Sift

Uncertain

0.0080

.;.;D;D;.;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

0.94, 0.19, 0.91

.;P;B;P;.;.

Vest4

0.54, 0.56, 0.57, 0.55, 0.56

MutPred

0.41

Gain of methylation at K59 (P = 0.0609);Gain of methylation at K59 (P = 0.0609);Gain of methylation at K59 (P = 0.0609);Gain of methylation at K59 (P = 0.0609);Gain of methylation at K59 (P = 0.0609);Gain of methylation at K59 (P = 0.0609);

MVP

0.30

MPC

0.48

ClinPred

0.74

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.21

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over