1-27966563-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018053.4(XKR8):​c.551C>A​(p.Ala184Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

XKR8
NM_018053.4 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15
Variant links:
Genes affected
XKR8 (HGNC:25508): (XK related 8) Enables phospholipid scramblase activity. Involved in engulfment of apoptotic cell; phosphatidylserine exposure on apoptotic cell surface; and positive regulation of myoblast differentiation. Located 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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.906

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
XKR8NM_018053.4 linkc.551C>A p.Ala184Asp missense_variant Exon 3 of 3 ENST00000373884.6 NP_060523.2 Q9H6D3
XKR8XM_011541679.4 linkc.713C>A p.Ala238Asp missense_variant Exon 5 of 5 XP_011539981.1
XKR8XM_011541680.4 linkc.605C>A p.Ala202Asp missense_variant Exon 4 of 4 XP_011539982.1
XKR8XM_047423826.1 linkc.550C>A p.Pro184Thr missense_variant Exon 4 of 4 XP_047279782.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
XKR8ENST00000373884.6 linkc.551C>A p.Ala184Asp missense_variant Exon 3 of 3 1 NM_018053.4 ENSP00000362991.5 Q9H6D3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461850
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727226
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000468
Hom.:
0

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 22, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.551C>A (p.A184D) alteration is located in exon 3 (coding exon 3) of the XKR8 gene. This alteration results from a C to A substitution at nucleotide position 551, causing the alanine (A) at amino acid position 184 to be replaced by an aspartic acid (D). 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
0.43
BayesDel_addAF
Pathogenic
0.16
D
BayesDel_noAF
Uncertain
-0.010
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.33
T
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.79
T
M_CAP
Benign
0.068
D
MetaRNN
Pathogenic
0.91
D
MetaSVM
Benign
-0.48
T
MutationAssessor
Pathogenic
3.0
M
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-3.3
D
REVEL
Uncertain
0.36
Sift
Benign
0.037
D
Sift4G
Uncertain
0.052
T
Polyphen
0.84
P
Vest4
0.74
MutPred
0.80
Gain of relative solvent accessibility (P = 0.09);
MVP
0.64
MPC
1.4
ClinPred
0.98
D
GERP RS
4.2
Varity_R
0.67
gMVP
0.65

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: rs1638573956; hg19: chr1-28293074; API