17-61392109-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BS1_Supporting

The NM_017679.5(BCAS3):c.2726C>G(p.Pro909Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,318 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

BCAS3
NM_017679.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.37

Publications

1 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:

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;

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0000329 (5/152172) while in subpopulation AMR AF = 0.000262 (4/15286). AF 95% confidence interval is 0.0000888. There are 0 homozygotes in GnomAd4. There are 2 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017679.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCAS3	NM_017679.5	MANE Select	c.2726C>G	p.Pro909Arg	missense	Exon 24 of 24	NP_060149.3
BCAS3	NM_001353144.2		c.2861C>G	p.Pro954Arg	missense	Exon 26 of 26	NP_001340073.1
BCAS3	NM_001330413.2		c.2837C>G	p.Pro946Arg	missense	Exon 26 of 26	NP_001317342.1	Q9H6U6-8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCAS3	ENST00000407086.8	TSL:1 MANE Select	c.2726C>G	p.Pro909Arg	missense	Exon 24 of 24	ENSP00000385323.2	Q9H6U6-2
BCAS3	ENST00000390652.9	TSL:1	c.2771C>G	p.Pro924Arg	missense	Exon 25 of 25	ENSP00000375067.4	Q9H6U6-1
BCAS3	ENST00000589222.5	TSL:1	c.*96C>G		3_prime_UTR	Exon 26 of 26	ENSP00000466078.1	Q9H6U6-7

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000563

AC:

AN:

248804

AF XY:

0.0000592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.0000999

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1461146

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726868

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.000157

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000180

AC:

AN:

1111856

Other (OTH)

AF:

0.0000497

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.000262

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000901

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000496

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

Eigen

Uncertain

0.64

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.063

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.55

PhyloP100

7.4

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.80

MutPred

0.31

Gain of catalytic residue at P924 (P = 0.0245)

MVP

0.64

MPC

1.2

ClinPred

0.68

GERP RS

5.4

Varity_R

0.43

gMVP

0.62

Mutation Taster

=45/55

disease causing

(source)

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over