dbSNP rs759720810: BCAS3:p.Tyr223Cys (chr17-60889701-A-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_017679.5(BCAS3):c.668A>G(p.Tyr223Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000366 in 1,612,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

BCAS3
NM_017679.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.79

Publications

5 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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.815

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.668A>G	p.Tyr223Cys	missense	Exon 10 of 24	NP_060149.3
BCAS3	NM_001353144.2		c.668A>G	p.Tyr223Cys	missense	Exon 10 of 26	NP_001340073.1
BCAS3	NM_001330413.2		c.668A>G	p.Tyr223Cys	missense	Exon 10 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.668A>G	p.Tyr223Cys	missense	Exon 10 of 24	ENSP00000385323.2	Q9H6U6-2
BCAS3	ENST00000390652.9	TSL:1	c.668A>G	p.Tyr223Cys	missense	Exon 10 of 25	ENSP00000375067.4	Q9H6U6-1
BCAS3	ENST00000589222.5	TSL:1	c.668A>G	p.Tyr223Cys	missense	Exon 10 of 26	ENSP00000466078.1	Q9H6U6-7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00000802

AC:

AN:

249494

AF XY:

0.0000148

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000397

AC:

AN:

1460716

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

726706

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33438

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5152

European-Non Finnish (NFE)

AF:

0.0000513

AC:

AN:

1111690

Other (OTH)

AF:

0.0000166

AC:

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

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:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

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:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000828

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

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

Uncertain

0.46

BayesDel_addAF

Uncertain

0.087

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.034

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.2

PhyloP100

6.8

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-7.7

REVEL

Uncertain

0.43

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.88

MutPred

0.52

Gain of glycosylation at P224 (P = 0.1789)

MVP

0.54

MPC

1.3

ClinPred

0.99

GERP RS

4.9

Varity_R

0.75

gMVP

0.68

Mutation Taster

=63/37

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over