chr8-55103206-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_052898.2(XKR4):​c.718A>G​(p.Ser240Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

XKR4
NM_052898.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00600
Variant links:
Genes affected
XKR4 (HGNC:29394): (XK related 4) Enables phospholipid scramblase activity. Involved in phosphatidylserine exposure on apoptotic cell surface. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.059197813).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
XKR4NM_052898.2 linkuse as main transcriptc.718A>G p.Ser240Gly missense_variant 1/3 ENST00000327381.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XKR4ENST00000327381.7 linkuse as main transcriptc.718A>G p.Ser240Gly missense_variant 1/31 NM_052898.2 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 07, 2023The c.718A>G (p.S240G) alteration is located in exon 1 (coding exon 1) of the XKR4 gene. This alteration results from a A to G substitution at nucleotide position 718, causing the serine (S) at amino acid position 240 to be replaced by a glycine (G). 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
0.054
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
10
DANN
Benign
0.85
DEOGEN2
Benign
0.019
T;T
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.65
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.32
.;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.059
T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
-0.11
N;N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
0.18
N;.
REVEL
Benign
0.18
Sift
Benign
0.50
T;.
Sift4G
Benign
0.89
T;T
Polyphen
0.0
B;B
Vest4
0.054
MutPred
0.56
Loss of glycosylation at S240 (P = 0.0077);Loss of glycosylation at S240 (P = 0.0077);
MVP
0.13
MPC
0.59
ClinPred
0.094
T
GERP RS
-1.5
Varity_R
0.087
gMVP
0.25

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: chr8-56015766; API