chrX-100914880-C-T

Variant summary

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

The NM_212559.3(XKRX):​c.808G>A​(p.Val270Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000082 in 1,098,221 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000082 ( 0 hom. 3 hem. )

Consequence

XKRX
NM_212559.3 missense

Scores

4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71
Variant links:
Genes affected
XKRX (HGNC:29845): (XK related X-linked) This gene encodes a protein that is related to a component of the XK/Kell complex of the Kell blood group system. The encoded protein includes several transmembrane domains, is known to be exposed to the cell surface, and may function as a membrane transporter. [provided by RefSeq, May 2010]

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=0.14504778).
BS2
High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
XKRXNM_212559.3 linkc.808G>A p.Val270Met missense_variant Exon 3 of 3 ENST00000372956.3 NP_997724.2 Q6PP77-1
XKRXXM_011530954.4 linkc.847G>A p.Val283Met missense_variant Exon 3 of 4 XP_011529256.1
XKRXXM_011530955.2 linkc.460G>A p.Val154Met missense_variant Exon 4 of 4 XP_011529257.1
XKRXXM_017029517.2 linkc.196G>A p.Val66Met missense_variant Exon 2 of 2 XP_016885006.1 Q6PP77-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
XKRXENST00000372956.3 linkc.808G>A p.Val270Met missense_variant Exon 3 of 3 1 NM_212559.3 ENSP00000362047.2 Q6PP77-1
XKRXENST00000468904 linkc.*119G>A 3_prime_UTR_variant Exon 2 of 2 2 ENSP00000419884.1 C9JYI8

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
0.00000820
AC:
9
AN:
1098221
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
3
AN XY:
363575
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000284
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:
0.00000831
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
Cov.:
23

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.808G>A (p.V270M) alteration is located in exon 3 (coding exon 3) of the XKRX gene. This alteration results from a G to A substitution at nucleotide position 808, causing the valine (V) at amino acid position 270 to be replaced by a methionine (M). 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
0.14
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.023
T
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.80
T
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.97
L
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-0.39
N
REVEL
Benign
0.12
Sift
Uncertain
0.014
D
Sift4G
Uncertain
0.043
D
Polyphen
0.041
B
Vest4
0.27
MutPred
0.54
Gain of ubiquitination at K268 (P = 0.1181);
MVP
0.23
MPC
0.17
ClinPred
0.43
T
GERP RS
2.5
Varity_R
0.16
gMVP
0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-100169869; API