X-15522470-G-C

Position:

chrX-15522470-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000348343.11(BMX):c.635G>C(p.Ser212Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000235 in 1,210,903 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 80 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.00025 ( 0 hom. 80 hem. )

Consequence

BMX
ENST00000348343.11 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.758

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.036927342).

BP6

Variant X-15522470-G-C is Benign according to our data. Variant chrX-15522470-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2367891.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 80 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMX	NM_203281.3 linkuse as main transcript	c.635G>C	p.Ser212Thr	missense_variant	7/19	ENST00000348343.11	NP_975010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMX	ENST00000348343.11 linkuse as main transcript	c.635G>C	p.Ser212Thr	missense_variant	7/19	1	NM_203281.3	ENSP00000308774	P1

Frequencies

GnomAD3 genomes

AF:

0.0000798

AC:

AN:

112746

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34914

show subpopulations

Gnomad AFR

AF:

0.0000322

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:

0.000150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000109

AC:

AN:

183081

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

67707

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000125

Gnomad NFE exome

AF:

0.000208

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000251

AC:

276

AN:

1098157

Hom.:

Cov.:

AF XY:

0.000220

AC XY:

AN XY:

363547

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000987

Gnomad4 NFE exome

AF:

0.000299

Gnomad4 OTH exome

AF:

0.000369

GnomAD4 genome

AF:

0.0000798

AC:

AN:

112746

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34914

show subpopulations

Gnomad4 AFR

AF:

0.0000322

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000150

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000904

Hom.:

Bravo

AF:

0.000110

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000437

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.24

DANN

Benign

0.21

DEOGEN2

Benign

0.11

T;T;T

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.19

.;.;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.037

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

0.26

N;N;N

REVEL

Benign

0.074

Sift

Benign

0.63

T;T;T

Sift4G

Benign

0.57

T;T;T

Polyphen

0.14

B;B;B

Vest4

0.078

MVP

0.46

MPC

0.31

ClinPred

0.030

GERP RS

-0.47

Varity_R

0.15

gMVP

0.055

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over