22-16784304-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001386955.1(XKR3):​c.695C>A​(p.Pro232Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 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. P232L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

XKR3
NM_001386955.1 missense

Scores

1
1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.62
Variant links:
Genes affected
XKR3 (HGNC:28778): (XK related 3) XKRX (MIM 300684) and XKR3 are homologs of the Kell blood group precursor XK (MIM 314850), which is a putative membrane transporter and a component of the XK/Kell complex of the Kell blood group system (Calenda et al., 2006 [PubMed 16431037]).[supplied by OMIM, Mar 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38051078).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
XKR3NM_001386955.1 linkc.695C>A p.Pro232Gln missense_variant 4/4 ENST00000684488.1 NP_001373884.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
XKR3ENST00000684488.1 linkc.695C>A p.Pro232Gln missense_variant 4/4 NM_001386955.1 ENSP00000507478.1 Q5GH77
XKR3ENST00000331428.5 linkc.695C>A p.Pro232Gln missense_variant 4/41 ENSP00000331704.5 Q5GH77

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
51
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.080
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
15
DANN
Benign
0.97
DEOGEN2
Benign
0.18
T
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.64
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.29
T
M_CAP
Benign
0.0064
T
MetaRNN
Benign
0.38
T
MetaSVM
Benign
-0.78
T
MutationAssessor
Benign
1.4
L
PROVEAN
Pathogenic
-4.6
D
REVEL
Benign
0.20
Sift
Benign
0.085
T
Sift4G
Uncertain
0.0090
D
Polyphen
1.0
D
Vest4
0.44
MutPred
0.52
Loss of loop (P = 0.0804);
MVP
0.44
MPC
3.1
ClinPred
0.79
D
GERP RS
-0.57
Varity_R
0.10
gMVP
0.089

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: rs9605146; hg19: chr22-17265194; API