rs202245028

Variant names:

• chrX-15522394-T-C
• rs202245028
• NM_203281.3:c.559T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_203281.3(BMX):​c.559T>C​(p.Ser187Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,210,497 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 43 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 0.00012 (0 hom., 6 hem., cov: 23)
  • Exomes 𝑓: 0.000098 (0 hom. 37 hem.)
• Consequence: BMX NM_203281.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26
• 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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.038844317).
• BS2: High Hemizygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203281.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMX	NM_203281.3	MANE Select	c.559T>C	p.Ser187Pro	missense	Exon 7 of 19	NP_975010.1	P51813
	BMX	NM_001721.7		c.559T>C	p.Ser187Pro	missense	Exon 7 of 19	NP_001712.1	P51813
	BMX	NM_001320866.2		c.559T>C	p.Ser187Pro	missense	Exon 7 of 19	NP_001307795.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMX	ENST00000348343.11	TSL:1 MANE Select	c.559T>C	p.Ser187Pro	missense	Exon 7 of 19	ENSP00000308774.6	P51813
	BMX	ENST00000342014.6	TSL:1	c.559T>C	p.Ser187Pro	missense	Exon 7 of 19	ENSP00000340082.6	P51813
	BMX	ENST00000357607.6	TSL:2	c.559T>C	p.Ser187Pro	missense	Exon 7 of 19	ENSP00000350224.2	P51813

Frequencies

GnomAD3 genomes AF: 0.000116 AC: 13 AN: 112412 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000945

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: 0.000225

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000819 AC: 15 AN: 183079 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

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: 0.000172

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.0000984 AC: 108 AN: 1098032 Hom.: 0 Cov.: 32 AF XY: 0.000102 AC XY: 37 AN XY: 363426

African (AFR) AF: 0.00 AC: 0 AN: 26394

American (AMR) AF: 0.0000284 AC: 1 AN: 35198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19379

East Asian (EAS) AF: 0.00 AC: 0 AN: 30197

South Asian (SAS) AF: 0.00 AC: 0 AN: 54137

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40532

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4135

European-Non Finnish (NFE) AF: 0.000122 AC: 103 AN: 841966

Other (OTH) AF: 0.0000651 AC: 3 AN: 46094

GnomAD4 genome AF: 0.000116 AC: 13 AN: 112465 Hom.: 0 Cov.: 23 AF XY: 0.000173 AC XY: 6 AN XY: 34639

African (AFR) AF: 0.00 AC: 0 AN: 31005

American (AMR) AF: 0.0000943 AC: 1 AN: 10600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3563

South Asian (SAS) AF: 0.00 AC: 0 AN: 2737

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6177

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.000225 AC: 12 AN: 53293

Other (OTH) AF: 0.00 AC: 0 AN: 1533

Alfa AF: 0.0000729 Hom.: 1

Bravo AF: 0.0000604

ExAC AF: 0.000115 AC: 14

EpiCase AF: 0.000327

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.85
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.3
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.76	N
REVEL	Benign	0.18
Sift	Benign	0.31	T
Sift4G	Benign	0.28	T
Polyphen		0.0010	B
Vest4		0.19
MVP		0.54
MPC		0.43
ClinPred		0.028	T
GERP RS		3.4
Varity_R		0.15
gMVP		0.39
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs202245028; hg19: chrX-15540517;