chr8-55102802-G-A

Variant summary

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

The NM_052898.2(XKR4):​c.314G>A​(p.Arg105Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000106 in 1,603,526 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 1 hom., cov: 31)
Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

XKR4
NM_052898.2 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.37
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=0.06524873).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
XKR4NM_052898.2 linkuse as main transcriptc.314G>A p.Arg105Gln missense_variant 1/3 ENST00000327381.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XKR4ENST00000327381.7 linkuse as main transcriptc.314G>A p.Arg105Gln missense_variant 1/31 NM_052898.2 P1

Frequencies

GnomAD3 genomes
AF:
0.0000396
AC:
6
AN:
151626
Hom.:
1
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000394
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000172
AC:
4
AN:
232716
Hom.:
0
AF XY:
0.0000156
AC XY:
2
AN XY:
128126
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000885
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000170
GnomAD4 exome
AF:
0.00000758
AC:
11
AN:
1451900
Hom.:
0
Cov.:
31
AF XY:
0.00000554
AC XY:
4
AN XY:
722628
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000135
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:
0.00000180
Gnomad4 OTH exome
AF:
0.0000498
GnomAD4 genome
AF:
0.0000396
AC:
6
AN:
151626
Hom.:
1
Cov.:
31
AF XY:
0.0000540
AC XY:
4
AN XY:
74048
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000394
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000852
Hom.:
0
Bravo
AF:
0.0000491

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 GeneticsFeb 28, 2024The c.314G>A (p.R105Q) alteration is located in exon 1 (coding exon 1) of the XKR4 gene. This alteration results from a G to A substitution at nucleotide position 314, causing the arginine (R) at amino acid position 105 to be replaced by a glutamine (Q). 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
0.065
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
24
DANN
Benign
0.97
DEOGEN2
Benign
0.022
T;T
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.12
FATHMM_MKL
Benign
0.024
N
LIST_S2
Benign
0.80
.;T
M_CAP
Pathogenic
0.45
D
MetaRNN
Benign
0.065
T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
-0.63
N;N
MutationTaster
Benign
1.0
N
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
0.44
N;.
REVEL
Benign
0.22
Sift
Benign
0.82
T;.
Sift4G
Benign
1.0
T;T
Polyphen
0.0
B;B
Vest4
0.11
MutPred
0.43
Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);
MVP
0.043
MPC
0.74
ClinPred
0.15
T
GERP RS
3.8
Varity_R
0.10
gMVP
0.13

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: rs893409248; hg19: chr8-56015362; API