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GeneBe

X-37686018-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_021083.4(XK):c.57G>C(p.Thr19=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,207,741 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 85 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., 1 hem., cov: 25)
Exomes 𝑓: 0.00021 ( 0 hom. 84 hem. )

Consequence

XK
NM_021083.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.38
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-37686018-G-C is Benign according to our data. Variant chrX-37686018-G-C is described in ClinVar as [Benign]. Clinvar id is 1573329.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-37686018-G-C is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.38 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Hemizygotes in GnomAdExome at 5 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
XKNM_021083.4 linkuse as main transcriptc.57G>C p.Thr19= synonymous_variant 1/3 ENST00000378616.5
XKXM_011543978.4 linkuse as main transcriptc.57G>C p.Thr19= synonymous_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XKENST00000378616.5 linkuse as main transcriptc.57G>C p.Thr19= synonymous_variant 1/31 NM_021083.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000140
AC:
16
AN:
113963
Hom.:
0
Cov.:
25
AF XY:
0.0000277
AC XY:
1
AN XY:
36079
show subpopulations
Gnomad AFR
AF:
0.0000317
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000183
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:
0.000243
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000142
AC:
24
AN:
169595
Hom.:
0
AF XY:
0.0000848
AC XY:
5
AN XY:
58943
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000747
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:
0.000283
Gnomad OTH exome
AF:
0.000238
GnomAD4 exome
AF:
0.000215
AC:
235
AN:
1093778
Hom.:
0
Cov.:
31
AF XY:
0.000233
AC XY:
84
AN XY:
360264
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000286
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:
0.000271
Gnomad4 OTH exome
AF:
0.000109
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000140
AC:
16
AN:
113963
Hom.:
0
Cov.:
25
AF XY:
0.0000277
AC XY:
1
AN XY:
36079
show subpopulations
Gnomad4 AFR
AF:
0.0000317
Gnomad4 AMR
AF:
0.000183
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000243
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
1
Bravo
AF:
0.000151

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeOct 04, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
Cadd
Benign
6.1
Dann
Benign
0.88
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8

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.

Other links and lift over

dbSNP: rs146718567; hg19: chrX-37545271; API