chr8-55102927-C-A
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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
NM_052898.2 missense
Scores
2
13
4
Clinical Significance
Conservation
PhyloP100: 3.66
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XKR4 | NM_052898.2 | c.439C>A | p.Leu147Ile | missense_variant | 1/3 | ENST00000327381.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XKR4 | ENST00000327381.7 | c.439C>A | p.Leu147Ile | missense_variant | 1/3 | 1 | NM_052898.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152222Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000203 AC: 5AN: 246436Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134264
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GnomAD4 exome AF: 0.0000370 AC: 54AN: 1459410Hom.: 0 Cov.: 31 AF XY: 0.0000386 AC XY: 28AN XY: 726160
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GnomAD4 genome AF: 0.0000459 AC: 7AN: 152340Hom.: 0 Cov.: 31 AF XY: 0.0000671 AC XY: 5AN XY: 74488
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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 | Dec 21, 2022 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
.;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Uncertain
D;.
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Gain of MoRF binding (P = 0.0838);Gain of MoRF binding (P = 0.0838);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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