22-16820953-A-G

Position:

• chr22-16820953-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386955.1(XKR3):​c.-11+4338T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 151,978 control chromosomes in the GnomAD database, including 49,741 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (49741 hom., cov: 30)
• Consequence: XKR3 NM_001386955.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.831

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XKR3	NM_001386955.1	c.-11+4338T>C		intron_variant		ENST00000684488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XKR3	ENST00000684488.1	c.-11+4338T>C		intron_variant			NM_001386955.1	P1
XKR3	ENST00000331428.5	c.-11+654T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122282 AN: 151862 Hom.: 49720 Cov.: 30

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.812

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.805 AC: 122352 AN: 151978 Hom.: 49741 Cov.: 30 AF XY: 0.807 AC XY: 59951 AN XY: 74288

Gnomad4 AFR AF: 0.693

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.830

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.881

Gnomad4 NFE AF: 0.865

Gnomad4 OTH AF: 0.807

Alfa AF: 0.851 Hom.: 107268

Bravo AF: 0.796

Asia WGS AF: 0.761 AC: 2639 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.62
DANN	Benign	0.27

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: rs874836; hg19: chr22-17301843;