chr8-55102802-G-A
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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
NM_052898.2 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 4.37
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 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 |
---|---|---|---|---|---|---|---|
XKR4 | NM_052898.2 | c.314G>A | p.Arg105Gln | missense_variant | 1/3 | ENST00000327381.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XKR4 | ENST00000327381.7 | c.314G>A | p.Arg105Gln | missense_variant | 1/3 | 1 | NM_052898.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000396 AC: 6AN: 151626Hom.: 1 Cov.: 31
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GnomAD3 exomes AF: 0.0000172 AC: 4AN: 232716Hom.: 0 AF XY: 0.0000156 AC XY: 2AN XY: 128126
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GnomAD4 exome AF: 0.00000758 AC: 11AN: 1451900Hom.: 0 Cov.: 31 AF XY: 0.00000554 AC XY: 4AN XY: 722628
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GnomAD4 genome AF: 0.0000396 AC: 6AN: 151626Hom.: 1 Cov.: 31 AF XY: 0.0000540 AC XY: 4AN XY: 74048
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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 submitter | clinical testing | Ambry Genetics | Feb 28, 2024 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;T
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);
MVP
MPC
ClinPred
T
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at