chr8-55102927-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052898.2(XKR4):​c.439C>A​(p.Leu147Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000378 in 1,611,750 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

XKR4
NM_052898.2 missense

Scores

2
13
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.66
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
XKR4NM_052898.2 linkuse as main transcriptc.439C>A p.Leu147Ile missense_variant 1/3 ENST00000327381.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XKR4ENST00000327381.7 linkuse as main transcriptc.439C>A p.Leu147Ile missense_variant 1/31 NM_052898.2 P1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152222
Hom.:
0
Cov.:
31
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:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000203
AC:
5
AN:
246436
Hom.:
0
AF XY:
0.0000223
AC XY:
3
AN XY:
134264
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000361
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000370
AC:
54
AN:
1459410
Hom.:
0
Cov.:
31
AF XY:
0.0000386
AC XY:
28
AN XY:
726160
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:
0.0000459
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000459
AC:
7
AN:
152340
Hom.:
0
Cov.:
31
AF XY:
0.0000671
AC XY:
5
AN XY:
74488
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:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000165
AC:
2

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 GeneticsDec 21, 2022The c.439C>A (p.L147I) alteration is located in exon 1 (coding exon 1) of the XKR4 gene. This alteration results from a C to A substitution at nucleotide position 439, causing the leucine (L) at amino acid position 147 to be replaced by an isoleucine (I). 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
Uncertain
0.52
BayesDel_addAF
Uncertain
0.072
D
BayesDel_noAF
Uncertain
-0.020
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T;T
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Benign
0.20
N
LIST_S2
Uncertain
0.97
.;D
M_CAP
Pathogenic
0.37
D
MetaRNN
Uncertain
0.74
D;D
MetaSVM
Uncertain
-0.10
T
MutationAssessor
Uncertain
2.3
M;M
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-0.99
N;.
REVEL
Uncertain
0.49
Sift
Uncertain
0.0080
D;.
Sift4G
Uncertain
0.0090
D;D
Polyphen
1.0
D;D
Vest4
0.61
MutPred
0.84
Gain of MoRF binding (P = 0.0838);Gain of MoRF binding (P = 0.0838);
MVP
0.59
MPC
1.5
ClinPred
0.48
T
GERP RS
5.3
Varity_R
0.42
gMVP
0.56

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: rs573625053; hg19: chr8-56015487; API