chr8-55102655-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052898.2(XKR4):​c.167C>T​(p.Pro56Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000313 in 1,279,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P56R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

XKR4
NM_052898.2 missense

Scores

2
1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.112329334).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
XKR4NM_052898.2 linkc.167C>T p.Pro56Leu missense_variant Exon 1 of 3 ENST00000327381.7 NP_443130.1 Q5GH76

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
XKR4ENST00000327381.7 linkc.167C>T p.Pro56Leu missense_variant Exon 1 of 3 1 NM_052898.2 ENSP00000328326.5 Q5GH76

Frequencies

GnomAD3 genomes
AF:
0.00000668
AC:
1
AN:
149612
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000149
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000377
AC:
2
AN:
53106
Hom.:
0
AF XY:
0.0000664
AC XY:
2
AN XY:
30106
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000798
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000265
AC:
3
AN:
1130132
Hom.:
0
Cov.:
30
AF XY:
0.00000552
AC XY:
3
AN XY:
543542
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:
0.00000320
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000668
AC:
1
AN:
149718
Hom.:
0
Cov.:
31
AF XY:
0.0000137
AC XY:
1
AN XY:
73154
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:
0.0000149
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000185
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Benign
0.029
T;T
Eigen
Benign
-0.50
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.019
N
LIST_S2
Benign
0.48
.;T
M_CAP
Pathogenic
0.80
D
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-0.62
T
MutationAssessor
Benign
0.34
N;N
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-0.61
N;.
REVEL
Benign
0.19
Sift
Benign
0.050
D;.
Sift4G
Benign
0.062
T;T
Polyphen
0.015
B;B
Vest4
0.19
MutPred
0.32
Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP
0.082
MPC
0.65
ClinPred
0.069
T
GERP RS
2.4
Varity_R
0.071
gMVP
0.19

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: rs557951243; hg19: chr8-56015215; API