dbSNP rs145716270: CPXCR1:p.Met263Thr (chrX-88754202-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_033048.6(CPXCR1):c.788T>C(p.Met263Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000583 in 1,187,048 control chromosomes in the GnomAD database, including 2 homozygotes. There are 199 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., 7 hem., cov: 23)

Exomes 𝑓: 0.00061 ( 2 hom. 192 hem. )

Consequence

CPXCR1
NM_033048.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.418

Publications

0 publications found

Variant links:

Genes affected

CPXCR1 (HGNC:2332): (CPX chromosome region candidate 1) This gene is one of several genes identified in a region of the X chromosome associated with an X-linked cleft palate (CPX) disorder. The encoded protein contains a motif similar to a motif found in zinc-finger proteins. Mutation analysis of this gene has not revealed any mutation which causes the CPX disorder. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2011]

CPXCR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.074308336).

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPXCR1	NM_033048.6 link	c.788T>C	p.Met263Thr	missense_variant	Exon 3 of 3	ENST00000276127.9	NP_149037.5	Q8N123
CPXCR1	NM_001184771.2 link	c.788T>C	p.Met263Thr	missense_variant	Exon 3 of 3		NP_001171700.2	Q8N123

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CPXCR1	ENST00000276127.9 link	c.788T>C	p.Met263Thr	missense_variant	Exon 3 of 3	1	NM_033048.6	ENSP00000276127.4	Q8N123
CPXCR1	ENST00000373111.5 link	c.788T>C	p.Met263Thr	missense_variant	Exon 3 of 3	2		ENSP00000362203.1	Q8N123
CPXCR1	ENST00000614120.1 link	c.788T>C	p.Met263Thr	missense_variant	Exon 2 of 2	3		ENSP00000484986.1	Q8N123

Frequencies

GnomAD3 genomes

AF:

0.000287

AC:

AN:

111650

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000191

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:

0.000545

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000198

AC:

AN:

176673

AF XY:

0.000259

show subpopulations

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:

0.000434

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.000614

AC:

660

AN:

1075398

Hom.:

Cov.:

AF XY:

0.000560

AC XY:

192

AN XY:

342878

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25964

American (AMR)

AF:

0.00

AC:

AN:

34822

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19117

East Asian (EAS)

AF:

0.00

AC:

AN:

29992

South Asian (SAS)

AF:

0.00

AC:

AN:

53140

European-Finnish (FIN)

AF:

0.0000248

AC:

AN:

40359

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4062

European-Non Finnish (NFE)

AF:

0.000765

AC:

629

AN:

822686

Other (OTH)

AF:

0.000663

AC:

AN:

45256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000287

AC:

AN:

111650

Hom.:

Cov.:

AF XY:

0.000207

AC XY:

AN XY:

33804

show subpopulations

African (AFR)

AF:

0.0000326

AC:

AN:

30703

American (AMR)

AF:

0.000191

AC:

AN:

10446

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3555

South Asian (SAS)

AF:

0.00

AC:

AN:

2659

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6021

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.000545

AC:

AN:

53180

Other (OTH)

AF:

0.00

AC:

AN:

1515

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000329

Hom.:

Bravo

AF:

0.000321

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00119

AC:

ExAC

AF:

0.000239

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 25, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.788T>C (p.M263T) alteration is located in exon 3 (coding exon 1) of the CPXCR1 gene. This alteration results from a T to C substitution at nucleotide position 788, causing the methionine (M) at amino acid position 263 to be replaced by a threonine (T). 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

Benign

0.18

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.4

(source)

DANN

Benign

0.34

DEOGEN2

Benign

0.025

T;T;T

FATHMM_MKL

Benign

0.0051

LIST_S2

Benign

0.29

.;.;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.074

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

N;N;N

PhyloP100

-0.42

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.0

D;D;.

REVEL

Benign

0.023

Sift

Benign

0.060

T;T;.

Sift4G

Benign

0.064

T;T;T

Polyphen

0.0070

B;B;B

Vest4

0.39

MVP

0.12

MPC

0.0093

ClinPred

0.013

GERP RS

-2.0

Varity_R

0.22

gMVP

0.085

Mutation Taster

=100/0

polymorphism

(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.

rs145716270

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over