rs147917241

Variant names:

• chrX-15522470-G-C
• rs147917241
• NM_203281.3:c.635G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-15522470-G-C
• chrX-15522470-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_203281.3(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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S212R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000080 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.00025 (0 hom. 80 hem.)
• Consequence: BMX NM_203281.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.758
• Publications: 0 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 -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 VariationId is 2367891.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 80 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.635G>C	p.Ser212Thr	missense	Exon 7 of 19	NP_975010.1	P51813
	BMX	NM_001721.7		c.635G>C	p.Ser212Thr	missense	Exon 7 of 19	NP_001712.1	P51813
	BMX	NM_001320866.2		c.635G>C	p.Ser212Thr	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.635G>C	p.Ser212Thr	missense	Exon 7 of 19	ENSP00000308774.6	P51813
	BMX	ENST00000342014.6	TSL:1	c.635G>C	p.Ser212Thr	missense	Exon 7 of 19	ENSP00000340082.6	P51813
	BMX	ENST00000357607.6	TSL:2	c.635G>C	p.Ser212Thr	missense	Exon 7 of 19	ENSP00000350224.2	P51813

Frequencies

GnomAD3 genomes AF: 0.0000798 AC: 9 AN: 112746 Hom.: 0 Cov.: 23

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

GnomAD2 exomes AF: 0.000109 AC: 20 AN: 183081 AF XY: 0.000133

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 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.: 0 Cov.: 32 AF XY: 0.000220 AC XY: 80 AN XY: 363547

African (AFR) AF: 0.0000379 AC: 1 AN: 26396

American (AMR) AF: 0.0000284 AC: 1 AN: 35193

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30202

South Asian (SAS) AF: 0.00 AC: 0 AN: 54148

European-Finnish (FIN) AF: 0.0000987 AC: 4 AN: 40531

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.000299 AC: 252 AN: 842079

Other (OTH) AF: 0.000369 AC: 17 AN: 46089

GnomAD4 genome AF: 0.0000798 AC: 9 AN: 112746 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34914

African (AFR) AF: 0.0000322 AC: 1 AN: 31026

American (AMR) AF: 0.00 AC: 0 AN: 10664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2661

East Asian (EAS) AF: 0.00 AC: 0 AN: 3594

South Asian (SAS) AF: 0.00 AC: 0 AN: 2755

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6239

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.000150 AC: 8 AN: 53359

Other (OTH) AF: 0.00 AC: 0 AN: 1522

Alfa AF: 0.0000904 Hom.: 1

Bravo AF: 0.000110

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.000437

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.060
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.24
DANN	Benign	0.21
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.76
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.074
Sift	Benign	0.63	T
Sift4G	Benign	0.57	T
Polyphen		0.14	B
Vest4		0.078
MVP		0.46
MPC		0.31
ClinPred		0.030	T
GERP RS		-0.47
Varity_R		0.15
gMVP		0.055
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs147917241; hg19: chrX-15540593;