22-16784304-G-T

Position:

• chr22-16784304-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

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]

ACMG classification

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
XKR3	NM_001386955.1	c.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
XKR3	ENST00000684488.1	c.695C>A	p.Pro232Gln	missense_variant	4/4		NM_001386955.1	ENSP00000507478.1
XKR3	ENST00000331428.5	c.695C>A	p.Pro232Gln	missense_variant	4/4	1		ENSP00000331704.5

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

Other links and lift over

dbSNP: rs9605146; hg19: chr22-17265194;