17-61040857-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017679.5(BCAS3):​c.1994A>G​(p.Asp665Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

BCAS3
NM_017679.5 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95
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-AS1 (HGNC:56376): (BCAS3 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.4165363).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BCAS3NM_017679.5 linkc.1994A>G p.Asp665Gly missense_variant Exon 19 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.1994A>G p.Asp665Gly missense_variant Exon 19 of 24 1 NM_017679.5 ENSP00000385323.2 Q9H6U6-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Nov 08, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2039A>G (p.D680G) alteration is located in exon 20 (coding exon 19) of the BCAS3 gene. This alteration results from a A to G substitution at nucleotide position 2039, causing the aspartic acid (D) at amino acid position 680 to be replaced by a glycine (G). 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
Uncertain
0.54
BayesDel_addAF
Uncertain
0.044
T
BayesDel_noAF
Benign
-0.18
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
.;.;T;.;.;T;.
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D;D;D;D;D;D;D
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.42
T;T;T;T;T;T;T
MetaSVM
Benign
-0.54
T
MutationAssessor
Benign
1.9
.;.;L;L;.;.;.
PrimateAI
Uncertain
0.69
T
PROVEAN
Uncertain
-2.6
.;D;D;.;D;.;.
REVEL
Benign
0.19
Sift
Benign
0.14
.;T;T;.;T;.;.
Sift4G
Uncertain
0.023
D;D;D;D;D;D;D
Polyphen
1.0
D;D;D;B;D;.;.
Vest4
0.59
MutPred
0.53
.;.;Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);.;.;.;
MVP
0.45
MPC
1.4
ClinPred
0.98
D
GERP RS
5.4
Varity_R
0.48
gMVP
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-59118218; API