Genetic Variant CXorf38:p.Glu157Gln (chrX-40639011-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_144970.3(CXorf38):c.469G>C(p.Glu157Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000215 in 1,209,459 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 88 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.00021 ( 0 hom. 84 hem. )

Consequence

CXorf38
NM_144970.3 missense, splice_region

Scores

Splicing: ADA: 0.5466

Clinical Significance

Uncertain significance no assertion criteria provided U:2

Conservation

PhyloP100: 4.14

Variant links:

Genes affected

CXorf38 (HGNC:28589): (chromosome X open reading frame 38)

CXorf38 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14113665).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXorf38	NM_144970.3 link	c.469G>C	p.Glu157Gln	missense_variant, splice_region_variant	Exon 3 of 7	ENST00000327877.10	NP_659407.1	Q8TB03-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CXorf38	ENST00000327877.10 link	c.469G>C	p.Glu157Gln	missense_variant, splice_region_variant	Exon 3 of 7	1	NM_144970.3	ENSP00000330488.5	Q8TB03-1
CXorf38	ENST00000378421.1 link	c.112G>C	p.Glu38Gln	missense_variant, splice_region_variant	Exon 3 of 7	2		ENSP00000367677.1	Q8TB03-2
CXorf38	ENST00000378426.5 link	c.112G>C	p.Glu38Gln	missense_variant, splice_region_variant	Exon 2 of 5	2		ENSP00000367683.1	Q8TB03-2

Frequencies

GnomAD3 genomes

AF:

0.000259

AC:

AN:

112138

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34292

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000190

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:

0.000488

Gnomad OTH

AF:

0.000668

GnomAD3 exomes

AF:

0.000171

AC:

AN:

180884

Hom.:

AF XY:

0.000214

AC XY:

AN XY:

65430

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000111

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000215

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000297

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000211

AC:

232

AN:

1097267

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

AN XY:

362691

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000569

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000241

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000217

Gnomad4 OTH exome

AF:

0.000499

GnomAD4 genome

AF:

0.000250

AC:

AN:

112192

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

34356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000488

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000373

Hom.:

Bravo

AF:

0.000253

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.000148

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

.;T;.

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.62

.;T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.1

.;M;.

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.079

Sift

Benign

0.036

D;T;D

Sift4G

Benign

0.064

T;D;T

Polyphen

0.93

.;P;.

Vest4

0.21

MVP

0.19

MPC

1.1

ClinPred

0.068

GERP RS

4.3

Varity_R

0.32

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.55

dbscSNV1_RF

Benign

0.59

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