NM_017679.5:c.68G>A

Variant summary

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

The NM_017679.5(BCAS3):​c.68G>A​(p.Arg23His) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,612,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R23L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

BCAS3
NM_017679.5 missense

Scores

3
5
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.32

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 Gene-Disease associations (from GenCC):
  • Hengel-Maroofian-Schols syndrome
    Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

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=0.32657814).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BCAS3NM_017679.5 linkc.68G>A p.Arg23His missense_variant Exon 2 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.68G>A p.Arg23His missense_variant Exon 2 of 24 1 NM_017679.5 ENSP00000385323.2 Q9H6U6-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152148
Hom.:
0
Cov.:
32
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:
0.00000401
AC:
1
AN:
249104
AF XY:
0.00000740
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000292
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:
0.00000411
AC:
6
AN:
1460590
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
726620
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33456
American (AMR)
AF:
0.0000224
AC:
1
AN:
44662
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26124
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39676
South Asian (SAS)
AF:
0.0000232
AC:
2
AN:
86124
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53412
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1111004
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60366
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.442
Heterozygous variant carriers
0
1
1
2
2
3
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:
0.00000657
AC:
1
AN:
152148
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74310
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41420
American (AMR)
AF:
0.00
AC:
0
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5188
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10606
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68042
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000828
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.56
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.35
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.072
T;.;T;.;T;.;.;.
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Pathogenic
0.99
D;D;D;D;D;D;D;D
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.33
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
2.0
.;M;.;M;M;.;M;M
PhyloP100
6.3
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.5
.;.;.;N;N;.;.;N
REVEL
Benign
0.14
Sift
Benign
0.13
.;.;.;T;T;.;.;T
Sift4G
Pathogenic
0.0
D;T;D;T;T;.;T;T
Polyphen
1.0, 1.0
.;D;.;D;D;.;.;.
Vest4
0.68, 0.84, 0.67, 0.67, 0.69, 0.69
MutPred
0.34
Loss of MoRF binding (P = 0.011);Loss of MoRF binding (P = 0.011);Loss of MoRF binding (P = 0.011);Loss of MoRF binding (P = 0.011);Loss of MoRF binding (P = 0.011);Loss of MoRF binding (P = 0.011);Loss of MoRF binding (P = 0.011);Loss of MoRF binding (P = 0.011);
MVP
0.43
MPC
1.3
ClinPred
0.77
D
GERP RS
4.2
PromoterAI
0.016
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.17
gMVP
0.46
Mutation Taster
=71/29
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs755073133; hg19: chr17-58756886; COSMIC: COSV66778193; API