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GeneBe

8-55523851-G-A

Variant summary

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

The NM_052898.2(XKR4):c.1577G>A(p.Cys526Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

XKR4
NM_052898.2 missense

Scores

8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.71
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]

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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=0.2560879).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
XKR4NM_052898.2 linkuse as main transcriptc.1577G>A p.Cys526Tyr missense_variant 3/3 ENST00000327381.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XKR4ENST00000327381.7 linkuse as main transcriptc.1577G>A p.Cys526Tyr missense_variant 3/31 NM_052898.2 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 14, 2023The c.1577G>A (p.C526Y) alteration is located in exon 3 (coding exon 3) of the XKR4 gene. This alteration results from a G to A substitution at nucleotide position 1577, causing the cysteine (C) at amino acid position 526 to be replaced by a tyrosine (Y). 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
0.20
BayesDel_addAF
Benign
-0.0035
T
BayesDel_noAF
Benign
-0.24
Cadd
Uncertain
25
Dann
Uncertain
0.99
DEOGEN2
Benign
0.22
T;T
Eigen
Benign
0.033
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.97
D
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.26
T;T
MetaSVM
Benign
-0.35
T
MutationAssessor
Uncertain
2.0
M;M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-3.8
D;.
REVEL
Uncertain
0.31
Sift
Uncertain
0.0040
D;.
Sift4G
Uncertain
0.037
D;D
Polyphen
0.011
B;B
Vest4
0.54
MutPred
0.28
Gain of phosphorylation at C526 (P = 0.0248);Gain of phosphorylation at C526 (P = 0.0248);
MVP
0.39
MPC
1.7
ClinPred
0.99
D
GERP RS
5.1
Varity_R
0.52
gMVP
0.86

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: chr8-56436410; API