chrX-37686046-C-G

Position:

• chrX-37686046-C-G

Variant summary

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

The NM_021083.4(XK):​c.85C>G​(p.Arg29Gly) variant causes a missense change involving the alteration of a non-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: 25)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: XK NM_021083.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0910

Genes affected

XK (HGNC:12811): (X-linked Kx blood group antigen, Kell and VPS13A binding protein) This locus controls the synthesis of the Kell blood group 'precursor substance' (Kx). Mutations in this gene have been associated with McLeod syndrome, an X-linked, recessive disorder characterized by abnormalities in the neuromuscular and hematopoietic systems. The encoded protein has structural characteristics of prokaryotic and eukaryotic membrane transport proteins. [provided by RefSeq, Jul 2008]

ENSG00000250349 (HGNC:):

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
XK	NM_021083.4	c.85C>G	p.Arg29Gly	missense_variant	1/3	ENST00000378616.5	NP_066569.1
XK	XM_011543978.4	c.85C>G	p.Arg29Gly	missense_variant	1/3		XP_011542280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XK	ENST00000378616.5	c.85C>G	p.Arg29Gly	missense_variant	1/3	1	NM_021083.4	ENSP00000367879.3
ENSG00000250349	ENST00000465127.1	c.171+260046C>G		intron_variant		5		ENSP00000417050.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.12e-7 AC: 1 AN: 1096480 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1 AN XY: 362376

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

McLeod neuroacanthocytosis syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Sep 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.72	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.25
Sift	Uncertain	0.015	D
Sift4G	Benign	0.15	T
Polyphen		0.55	P
Vest4		0.38
MutPred		0.65		Loss of methylation at R29 (P = 0.0268);
MVP		0.31
MPC		1.0
ClinPred		0.84	D
GERP RS		1.4
Varity_R		0.33
gMVP		0.65

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-37545299;