Variant X-37686111-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_021083.4(XK):c.150C>T(p.Leu50=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,210,630 control chromosomes in the GnomAD database, including 47 homozygotes. There are 933 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 20 hom., 464 hem., cov: 25)

Exomes 𝑓: 0.0015 ( 27 hom. 469 hem. )

Consequence

XK
NM_021083.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.564

Variant links:

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]

XK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant X-37686111-C-T is Benign according to our data. Variant chrX-37686111-C-T is described in ClinVar as [Benign]. Clinvar id is 695327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.564 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.014 (1593/113556) while in subpopulation AFR AF= 0.0481 (1507/31354). AF 95% confidence interval is 0.046. There are 20 homozygotes in gnomad4. There are 464 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XK	NM_021083.4 linkuse as main transcript	c.150C>T	p.Leu50=	synonymous_variant	1/3	ENST00000378616.5
XK	XM_011543978.4 linkuse as main transcript	c.150C>T	p.Leu50=	synonymous_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XK	ENST00000378616.5 linkuse as main transcript	c.150C>T	p.Leu50=	synonymous_variant	1/3	1	NM_021083.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

1587

AN:

113503

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

461

AN XY:

35643

show subpopulations

Gnomad AFR

AF:

0.0480

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00542

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000354

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0126

Gnomad NFE

AF:

0.000150

Gnomad OTH

AF:

0.00974

GnomAD3 exomes

AF:

0.00451

AC:

800

AN:

177528

Hom.:

AF XY:

0.00289

AC XY:

186

AN XY:

64350

show subpopulations

Gnomad AFR exome

AF:

0.0560

Gnomad AMR exome

AF:

0.00235

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000216

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000895

Gnomad OTH exome

AF:

0.00249

GnomAD4 exome

AF:

0.00155

AC:

1695

AN:

1097074

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

469

AN XY:

362692

show subpopulations

Gnomad4 AFR exome

AF:

0.0503

Gnomad4 AMR exome

AF:

0.00287

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000371

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000867

Gnomad4 OTH exome

AF:

0.00330

GnomAD4 genome

AF:

0.0140

AC:

1593

AN:

113556

Hom.:

Cov.:

AF XY:

0.0130

AC XY:

464

AN XY:

35706

show subpopulations

Gnomad4 AFR

AF:

0.0481

Gnomad4 AMR

AF:

0.00541

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000355

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000150

Gnomad4 OTH

AF:

0.00962

Alfa

AF:

0.00333

Hom.:

Bravo

AF:

0.0163

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 26, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 06, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

3.8

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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