chrX-139956185-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001013403.3(CXorf66):​c.797G>A​(p.Cys266Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 1,209,716 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.000013 ( 0 hom. 6 hem. )

Consequence

CXorf66
NM_001013403.3 missense

Scores

1
2
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.433
Variant links:
Genes affected
CXorf66 (HGNC:33743): (chromosome X open reading frame 66) The protein encoded by this gene is predicted to be a type I membrane protein, however, its exact function is not known. [provided by RefSeq, Sep 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CXorf66NM_001013403.3 linkc.797G>A p.Cys266Tyr missense_variant Exon 3 of 3 ENST00000370540.2 NP_001013421.1 Q5JRM2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CXorf66ENST00000370540.2 linkc.797G>A p.Cys266Tyr missense_variant Exon 3 of 3 1 NM_001013403.3 ENSP00000359571.1 Q5JRM2

Frequencies

GnomAD3 genomes
AF:
0.0000268
AC:
3
AN:
112011
Hom.:
0
Cov.:
23
AF XY:
0.0000293
AC XY:
1
AN XY:
34177
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000563
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000128
AC:
14
AN:
1097705
Hom.:
0
Cov.:
30
AF XY:
0.0000165
AC XY:
6
AN XY:
363063
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000166
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000268
AC:
3
AN:
112011
Hom.:
0
Cov.:
23
AF XY:
0.0000293
AC XY:
1
AN XY:
34177
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000563
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000611
Hom.:
2
Bravo
AF:
0.0000378
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000149
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 29, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.797G>A (p.C266Y) alteration is located in exon 3 (coding exon 3) of the CXorf66 gene. This alteration results from a G to A substitution at nucleotide position 797, causing the cysteine (C) at amino acid position 266 to be replaced by a tyrosine (Y). 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
0.17
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
12
DANN
Benign
0.95
DEOGEN2
Benign
0.12
T
FATHMM_MKL
Benign
0.051
N
LIST_S2
Benign
0.44
T
M_CAP
Benign
0.020
T
MetaRNN
Uncertain
0.58
D
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.1
L
PROVEAN
Pathogenic
-8.0
D
REVEL
Benign
0.10
Sift
Uncertain
0.015
D
Sift4G
Benign
0.28
T
Polyphen
1.0
D
Vest4
0.54
MVP
0.088
MPC
0.54
ClinPred
0.91
D
GERP RS
3.3
Varity_R
0.54
gMVP
0.34

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.

Other links and lift over

dbSNP: rs199917707; hg19: chrX-139038344; API