Variant X-2797355-C-A 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_001141919.2(XG):c.368C>A(p.Thr123Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,206,931 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 56 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000055 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.00015 ( 0 hom. 55 hem. )

Consequence

XG
NM_001141919.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.36

Variant links:

Genes affected

XG (HGNC:12806): (Xg glycoprotein (Xg blood group)) This gene encodes the XG blood group antigen, and is located at the pseudoautosomal boundary on the short (p) arm of chromosome X. The three 5' exons reside in the pseudoautosomal region and the remaining exons within the X-specific end. A truncated copy of this gene is found on the Y chromosome at the pseudoautosomal boundary. It is transcribed, but not expected to make a Y-chromosome specific gene product. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

XG links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09884307).

BS2

High Hemizygotes in GnomAdExome4 at 55 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XG	NM_001141919.2 linkuse as main transcript	c.368C>A	p.Thr123Lys	missense_variant	7/11	ENST00000644266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XG	ENST00000644266.2 linkuse as main transcript	c.368C>A	p.Thr123Lys	missense_variant	7/11		NM_001141919.2		P55808-3

Frequencies

GnomAD3 genomes

AF:

0.0000547

AC:

AN:

109765

Hom.:

Cov.:

AF XY:

0.0000312

AC XY:

AN XY:

32059

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000114

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000493

AC:

AN:

182690

Hom.:

AF XY:

0.0000447

AC XY:

AN XY:

67176

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.000110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000146

AC:

160

AN:

1097166

Hom.:

Cov.:

AF XY:

0.000152

AC XY:

AN XY:

362554

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:

0.000187

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.0000547

AC:

AN:

109765

Hom.:

Cov.:

AF XY:

0.0000312

AC XY:

AN XY:

32059

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000114

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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

Apr 12, 2024

The c.368C>A (p.T123K) alteration is located in exon 7 (coding exon 7) of the XG gene. This alteration results from a C to A substitution at nucleotide position 368, causing the threonine (T) at amino acid position 123 to be replaced by a lysine (K). 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

0.17

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.49

CADD

Benign

2.6

DANN

Benign

0.88

DEOGEN2

Benign

0.11

.;.;T;.

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.38

T;T;T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.099

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;.;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-3.1

.;D;N;.

REVEL

Benign

0.095

Sift

Pathogenic

0.0

.;D;D;.

Sift4G

Benign

0.067

.;T;T;.

Polyphen

0.97, 0.96

.;.;D;D

Vest4

0.38

MutPred

0.20

.;.;Gain of solvent accessibility (P = 0.007);Gain of solvent accessibility (P = 0.007);

MVP

0.061

MPC

0.14

ClinPred

0.061

GERP RS

1.4

Varity_R

0.34

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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