Variant X-100914916-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_212559.3(XKRX):c.772C>G(p.Leu258Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000728 in 1,098,228 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000073 ( 0 hom. 1 hem. )

Consequence

XKRX
NM_212559.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33

Variant links:

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]

XKRX links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.751

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKRX	NM_212559.3 linkuse as main transcript	c.772C>G	p.Leu258Val	missense_variant	3/3	ENST00000372956.3	NP_997724.2	Q6PP77-1
XKRX	XM_011530954.4 linkuse as main transcript	c.811C>G	p.Leu271Val	missense_variant	3/4		XP_011529256.1
XKRX	XM_011530955.2 linkuse as main transcript	c.424C>G	p.Leu142Val	missense_variant	4/4		XP_011529257.1
XKRX	XM_017029517.2 linkuse as main transcript	c.160C>G	p.Leu54Val	missense_variant	2/2		XP_016885006.1	Q6PP77-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKRX	ENST00000372956.3 linkuse as main transcript	c.772C>G	p.Leu258Val	missense_variant	3/3	1	NM_212559.3	ENSP00000362047.2		Q6PP77-1
XKRX	ENST00000468904.1 linkuse as main transcript	c.*83C>G		3_prime_UTR_variant	2/2	2		ENSP00000419884.1		C9JYI8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000728

AC:

AN:

1098228

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363584

show subpopulations

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:

0.00000950

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.772C>G (p.L258V) alteration is located in exon 3 (coding exon 3) of the XKRX gene. This alteration results from a C to G substitution at nucleotide position 772, causing the leucine (L) at amino acid position 258 to be replaced by a valine (V). 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

0.43

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.75

M_CAP

Benign

0.076

MetaRNN

Pathogenic

0.75

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.7

REVEL

Uncertain

0.52

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.95

Vest4

0.73

MutPred

0.78

Loss of stability (P = 0.1789);

MVP

0.21

MPC

0.51

ClinPred

0.97

GERP RS

2.8

Varity_R

0.84

gMVP

0.72

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over