Variant X-100914840-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_212559.3(XKRX):c.848A>G(p.Glu283Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,209,475 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. 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 0.00011 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.0000091 ( 0 hom. 0 hem. )

Consequence

XKRX
NM_212559.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31085142).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKRX	NM_212559.3 linkuse as main transcript	c.848A>G	p.Glu283Gly	missense_variant	3/3	ENST00000372956.3	NP_997724.2	Q6PP77-1
XKRX	XM_011530954.4 linkuse as main transcript	c.887A>G	p.Glu296Gly	missense_variant	3/4		XP_011529256.1
XKRX	XM_011530955.2 linkuse as main transcript	c.500A>G	p.Glu167Gly	missense_variant	4/4		XP_011529257.1
XKRX	XM_017029517.2 linkuse as main transcript	c.236A>G	p.Glu79Gly	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.848A>G	p.Glu283Gly	missense_variant	3/3	1	NM_212559.3	ENSP00000362047.2		Q6PP77-1
XKRX	ENST00000468904.1 linkuse as main transcript	c.*159A>G		3_prime_UTR_variant	2/2	2		ENSP00000419884.1		C9JYI8

Frequencies

GnomAD3 genomes

AF:

0.000108

AC:

AN:

111212

Hom.:

Cov.:

AF XY:

0.0000898

AC XY:

AN XY:

33404

show subpopulations

Gnomad AFR

AF:

0.000393

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

183294

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67790

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000911

AC:

AN:

1098263

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363617

show subpopulations

Gnomad4 AFR exome

AF:

0.000265

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:

0.00000237

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.000108

AC:

AN:

111212

Hom.:

Cov.:

AF XY:

0.0000898

AC XY:

AN XY:

33404

show subpopulations

Gnomad4 AFR

AF:

0.000393

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000166

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

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

Oct 06, 2024

The c.848A>G (p.E283G) alteration is located in exon 3 (coding exon 3) of the XKRX gene. This alteration results from a A to G substitution at nucleotide position 848, causing the glutamic acid (E) at amino acid position 283 to be replaced by a glycine (G). 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

0.45

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.69

M_CAP

Pathogenic

0.56

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.31

Sift

Benign

0.31

Sift4G

Benign

0.34

Polyphen

0.98

Vest4

0.37

MVP

0.47

MPC

0.55

ClinPred

0.15

GERP RS

5.5

Varity_R

0.27

gMVP

0.76

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