chrX-100914532-G-T

Position:

• chrX-100914532-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_212559.3(XKRX):​c.1156C>A​(p.Gln386Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: XKRX NM_212559.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.74

Genes affected

XKRX (HGNC:29845): (XK related X-linked) This gene encodes a protein that is related to a component of the XK/Kell complex of the Kell blood group system. The encoded protein includes several transmembrane domains, is known to be exposed to the cell surface, and may function as a membrane transporter. [provided by RefSeq, May 2010]

ACMG classification

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	Protein	UniProt
XKRX	NM_212559.3	c.1156C>A	p.Gln386Lys	missense_variant	3/3	ENST00000372956.3	NP_997724.2
XKRX	XM_011530955.2	c.808C>A	p.Gln270Lys	missense_variant	4/4		XP_011529257.1
XKRX	XM_017029517.2	c.544C>A	p.Gln182Lys	missense_variant	2/2		XP_016885006.1
XKRX	XM_011530954.4	c.1106+89C>A		intron_variant			XP_011529256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKRX	ENST00000372956.3	c.1156C>A	p.Gln386Lys	missense_variant	3/3	1	NM_212559.3	ENSP00000362047.2
XKRX	ENST00000468904.1	c.*467C>A		3_prime_UTR_variant	2/2	2		ENSP00000419884.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 16, 2024

The c.1156C>A (p.Q386K) alteration is located in exon 3 (coding exon 3) of the XKRX gene. This alteration results from a C to A substitution at nucleotide position 1156, causing the glutamine (Q) at amino acid position 386 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.43
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.55		Gain of ubiquitination at Q386 (P = 0.0258);
MVP		0.12
MPC		0.56
ClinPred		0.91	D
GERP RS		5.7
Varity_R		0.81
gMVP		0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-100169521;