Genetic Variant NM_017679.5:c.2489T>C (chr17-61368390-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017679.5(BCAS3):c.2489T>C(p.Leu830Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,486 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: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BCAS3
NM_017679.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.20

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 links:

TBX2-AS1 (HGNC:50355): (TBX2 antisense RNA 1)

TBX2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21565673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAS3	NM_017679.5 link	c.2489T>C	p.Leu830Pro	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.2489T>C	p.Leu830Pro	missense_variant	Exon 23 of 24	1	NM_017679.5	ENSP00000385323.2		Q9H6U6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460486

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110846

Other (OTH)

AF:

0.00

AC:

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Apr 25, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2534T>C (p.L845P) alteration is located in exon 24 (coding exon 23) of the BCAS3 gene. This alteration results from a T to C substitution at nucleotide position 2534, causing the leucine (L) at amino acid position 845 to be replaced by a proline (P). 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

0.26

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

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

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.86

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

M_CAP

Benign

0.019

MetaRNN

Benign

0.22

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

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

PhyloP100

5.2

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.26

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

REVEL

Benign

0.15

Sift

Benign

0.18

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

Sift4G

Benign

0.28

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

Polyphen

0.51

P;P;B;B;B;.;.;.

Vest4

0.38

MutPred

0.36

.;.;Loss of catalytic residue at L845 (P = 0.0123);Loss of catalytic residue at L845 (P = 0.0123);.;.;.;.;

MVP

0.12

MPC

0.99

ClinPred

0.83

GERP RS

4.8

Varity_R

0.29

gMVP

0.57

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