Variant chrX-100915072-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_212559.3(XKRX):c.616G>A(p.Val206Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000615 in 1,203,488 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000064 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000061 ( 0 hom. 14 hem. )

Consequence

XKRX
NM_212559.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.358

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08440822).

BS2

High Hemizygotes in GnomAdExome4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKRX	NM_212559.3 linkuse as main transcript	c.616G>A	p.Val206Ile	missense_variant	3/3	ENST00000372956.3	NP_997724.2	Q6PP77-1
XKRX	XM_011530954.4 linkuse as main transcript	c.655G>A	p.Val219Ile	missense_variant	3/4		XP_011529256.1
XKRX	XM_011530955.2 linkuse as main transcript	c.268G>A	p.Val90Ile	missense_variant	4/4		XP_011529257.1
XKRX	XM_017029517.2 linkuse as main transcript	c.4G>A	p.Val2Ile	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.616G>A	p.Val206Ile	missense_variant	3/3	1	NM_212559.3	ENSP00000362047.2		Q6PP77-1
XKRX	ENST00000468904.1 linkuse as main transcript	c.347G>A	p.Gly116Asp	missense_variant	2/2	2		ENSP00000419884.1		C9JYI8

Frequencies

GnomAD3 genomes

AF:

0.0000639

AC:

AN:

109571

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32061

show subpopulations

Gnomad AFR

AF:

0.0000345

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000194

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000753

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

179669

Hom.:

AF XY:

0.00

AC XY:

AN XY:

64799

show subpopulations

Gnomad AFR exome

AF:

0.0000778

Gnomad AMR exome

AF:

0.0000745

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000248

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000612

AC:

AN:

1093917

Hom.:

Cov.:

AF XY:

0.0000389

AC XY:

AN XY:

359725

show subpopulations

Gnomad4 AFR exome

AF:

0.0000381

Gnomad4 AMR exome

AF:

0.0000576

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:

0.0000750

Gnomad4 OTH exome

AF:

0.0000218

GnomAD4 genome

AF:

0.0000639

AC:

AN:

109571

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32061

show subpopulations

Gnomad4 AFR

AF:

0.0000345

Gnomad4 AMR

AF:

0.000194

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000753

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

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

Nov 21, 2024

The c.616G>A (p.V206I) alteration is located in exon 3 (coding exon 3) of the XKRX gene. This alteration results from a G to A substitution at nucleotide position 616, causing the valine (V) at amino acid position 206 to be replaced by an isoleucine (I). 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

Benign

0.076

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.63

CADD

Benign

7.1

DANN

Benign

0.69

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.37

M_CAP

Benign

0.038

MetaRNN

Benign

0.084

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.78

REVEL

Benign

0.043

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.031

Vest4

0.36

MVP

0.22

ClinPred

0.027

GERP RS

3.5

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over