NM_017679.5:c.2531G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4BS1_Supporting

The NM_017679.5(BCAS3):​c.2531G>A​(p.Arg844Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,612,360 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R844W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

BCAS3
NM_017679.5 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.49

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.39374775).
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000112 (17/152180) while in subpopulation AFR AF = 0.000362 (15/41454). AF 95% confidence interval is 0.000222. There are 0 homozygotes in GnomAd4. There are 9 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
BCAS3NM_017679.5 linkc.2531G>A p.Arg844Gln 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
BCAS3ENST00000407086.8 linkc.2531G>A p.Arg844Gln missense_variant Exon 23 of 24 1 NM_017679.5 ENSP00000385323.2 Q9H6U6-2

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000362
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:
0.000478
GnomAD2 exomes
AF:
0.0000201
AC:
5
AN:
249170
AF XY:
0.0000222
show subpopulations
Gnomad AFR exome
AF:
0.000259
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1460180
Hom.:
0
Cov.:
30
AF XY:
0.00000964
AC XY:
7
AN XY:
726046
show subpopulations
African (AFR)
AF:
0.0000897
AC:
3
AN:
33458
American (AMR)
AF:
0.00
AC:
0
AN:
44702
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26120
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39638
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86216
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53348
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
0.00000810
AC:
9
AN:
1110626
Other (OTH)
AF:
0.0000497
AC:
3
AN:
60314
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.456
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000112
AC:
17
AN:
152180
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74334
show subpopulations
African (AFR)
AF:
0.000362
AC:
15
AN:
41454
American (AMR)
AF:
0.00
AC:
0
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5174
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68030
Other (OTH)
AF:
0.000478
AC:
1
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000387
Hom.:
0
Bravo
AF:
0.0000604
ESP6500AA
AF:
0.000243
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000331
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Aug 27, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.2576G>A (p.R859Q) alteration is located in exon 24 (coding exon 23) of the BCAS3 gene. This alteration results from a G to A substitution at nucleotide position 2576, causing the arginine (R) at amino acid position 859 to be replaced by a glutamine (Q). 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
0.24
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.30
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.066
.;.;T;.;.;T;.
Eigen
Benign
0.12
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.96
D;D;D;D;D;D;D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.39
T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
.;.;N;N;.;.;.
PhyloP100
7.5
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-2.2
.;N;N;.;N;.;.
REVEL
Benign
0.19
Sift
Uncertain
0.017
.;D;D;.;D;.;.
Sift4G
Benign
0.22
T;T;T;T;T;T;T
Polyphen
0.46
P;P;B;P;P;.;.
Vest4
0.78
MVP
0.27
MPC
0.52
ClinPred
0.12
T
GERP RS
5.8
Varity_R
0.22
gMVP
0.55
Mutation Taster
=76/24
polymorphism

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

Other links and lift over

dbSNP: rs372094686; hg19: chr17-59445793; API