rs1171195833
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_203281.3(BMX):c.1186G>A(p.Ala396Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,206,394 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000091 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.0000036 ( 0 hom. 1 hem. )
Consequence
BMX
NM_203281.3 missense
NM_203281.3 missense
Scores
17
Clinical Significance
Conservation
PhyloP100: 0.781
Publications
1 publications found
Genes affected
BMX (HGNC:1079): (BMX non-receptor tyrosine kinase) This gene encodes a non-receptor tyrosine kinase belonging to the Tec kinase family. The protein contains a PH-like domain, which mediates membrane targeting by binding to phosphatidylinositol 3,4,5-triphosphate (PIP3), and a SH2 domain that binds to tyrosine-phosphorylated proteins and functions in signal transduction. The protein is implicated in several signal transduction pathways including the Stat pathway, and regulates differentiation and tumorigenicity of several types of cancer cells. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]
ACE2 (HGNC:13557): (angiotensin converting enzyme 2) The protein encoded by this gene belongs to the angiotensin-converting enzyme family of dipeptidyl carboxydipeptidases and has considerable homology to human angiotensin 1 converting enzyme. This secreted protein catalyzes the cleavage of angiotensin I into angiotensin 1-9, and angiotensin II into the vasodilator angiotensin 1-7. ACE2 is known to be expressed in various human organs, and its organ- and cell-specific expression suggests that it may play a role in the regulation of cardiovascular and renal function, as well as fertility. In addition, the encoded protein is a functional receptor for the spike glycoprotein of the human coronavirus HCoV-NL63 and the human severe acute respiratory syndrome coronaviruses, SARS-CoV and SARS-CoV-2, the latter is the causative agent of coronavirus disease-2019 (COVID-19). Multiple splice variants have been found for this gene and the dACE2 (or MIRb-ACE2) splice variant has been found to be interferon inducible. [provided by RefSeq, Nov 2020]
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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=0.06924528).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00000907 AC: 1AN: 110216Hom.: 0 Cov.: 22 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
110216
Hom.:
Cov.:
22
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000547 AC: 1AN: 182711 AF XY: 0.0000149 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
182711
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000365 AC: 4AN: 1096178Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 1AN XY: 361896 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1096178
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
361896
show subpopulations
African (AFR)
AF:
AC:
0
AN:
26346
American (AMR)
AF:
AC:
0
AN:
35147
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19326
East Asian (EAS)
AF:
AC:
4
AN:
30168
South Asian (SAS)
AF:
AC:
0
AN:
53818
European-Finnish (FIN)
AF:
AC:
0
AN:
40457
Middle Eastern (MID)
AF:
AC:
0
AN:
4130
European-Non Finnish (NFE)
AF:
AC:
0
AN:
840786
Other (OTH)
AF:
AC:
0
AN:
46000
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000907 AC: 1AN: 110216Hom.: 0 Cov.: 22 AF XY: 0.0000308 AC XY: 1AN XY: 32512 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
110216
Hom.:
Cov.:
22
AF XY:
AC XY:
1
AN XY:
32512
show subpopulations
African (AFR)
AF:
AC:
0
AN:
30244
American (AMR)
AF:
AC:
0
AN:
10288
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2629
East Asian (EAS)
AF:
AC:
1
AN:
3539
South Asian (SAS)
AF:
AC:
0
AN:
2579
European-Finnish (FIN)
AF:
AC:
0
AN:
5742
Middle Eastern (MID)
AF:
AC:
0
AN:
239
European-Non Finnish (NFE)
AF:
AC:
0
AN:
52781
Other (OTH)
AF:
AC:
0
AN:
1492
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Feb 20, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.1186G>A (p.A396T) alteration is located in exon 13 (coding exon 12) of the BMX gene. This alteration results from a G to A substitution at nucleotide position 1186, causing the alanine (A) at amino acid position 396 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Benign
T;T;T
FATHMM_MKL
Benign
D
LIST_S2
Benign
.;.;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N
PhyloP100
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;B;B
Vest4
MutPred
Gain of glycosylation at A396 (P = 0.0444);Gain of glycosylation at A396 (P = 0.0444);Gain of glycosylation at A396 (P = 0.0444);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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