X-15534277-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_203281.3(BMX):c.1085C>T(p.Ala362Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000268 in 1,194,565 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000027 ( 0 hom. 8 hem. )

Consequence

BMX
NM_203281.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03

Variant links:

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]

BMX links:

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]

ACE2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMX	NM_203281.3 link	c.1085C>T	p.Ala362Val	missense_variant	Exon 12 of 19	ENST00000348343.11	NP_975010.1	P51813

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMX	ENST00000348343.11 link	c.1085C>T	p.Ala362Val	missense_variant	Exon 12 of 19	1	NM_203281.3	ENSP00000308774.6		P51813

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

112039

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000648

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000118

AC:

AN:

169347

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000163

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:

0.0000268

AC:

AN:

1082526

Hom.:

Cov.:

AF XY:

0.0000228

AC XY:

AN XY:

350884

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25672

American (AMR)

AF:

0.00

AC:

AN:

33774

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19075

East Asian (EAS)

AF:

0.00

AC:

AN:

29487

South Asian (SAS)

AF:

0.00

AC:

AN:

51941

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4081

European-Non Finnish (NFE)

AF:

0.0000348

AC:

AN:

832655

Other (OTH)

AF:

0.00

AC:

AN:

45505

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000268

AC:

AN:

112039

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34217

show subpopulations

African (AFR)

AF:

0.0000648

AC:

AN:

30879

American (AMR)

AF:

0.00

AC:

AN:

10513

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3600

South Asian (SAS)

AF:

0.00

AC:

AN:

2721

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6071

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53172

Other (OTH)

AF:

0.00

AC:

AN:

1508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 10, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1085C>T (p.A362V) alteration is located in exon 12 (coding exon 11) of the BMX gene. This alteration results from a C to T substitution at nucleotide position 1085, causing the alanine (A) at amino acid position 362 to be replaced by a valine (V). 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

Pathogenic

0.77

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.73

D;D;D

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.86

.;.;D

M_CAP

Pathogenic

0.63

MetaRNN

Uncertain

0.63

D;D;D

MetaSVM

Uncertain

0.68

MutationAssessor

Uncertain

2.1

M;M;M

PhyloP100

5.0

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Pathogenic

0.72

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.50

MVP

0.93

MPC

0.65

ClinPred

0.77

GERP RS

5.1

Varity_R

0.72

gMVP

0.33

Mutation Taster

=48/52

disease causing

(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.

X-15534277-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over