Variant X-2811338-A-C 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.457A>C(p.Asn153His) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000582 in 1,202,475 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. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000055 ( 0 hom. 3 hem. )

Consequence

XG
NM_001141919.2 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.676

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:

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=0.087411135).

BS2

High Hemizygotes in GnomAdExome4 at 3 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XG	NM_001141919.2 linkuse as main transcript	c.457A>C	p.Asn153His	missense_variant, splice_region_variant	10/11	ENST00000644266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XG	ENST00000644266.2 linkuse as main transcript	c.457A>C	p.Asn153His	missense_variant, splice_region_variant	10/11		NM_001141919.2		P55808-3
XG	ENST00000381174.10 linkuse as main transcript	c.412A>C	p.Asn138His	missense_variant, splice_region_variant	9/10	1		P1	P55808-1
XG	ENST00000419513.7 linkuse as main transcript	c.391A>C	p.Asn131His	missense_variant, splice_region_variant	8/9	1
XG	ENST00000509484.3 linkuse as main transcript	c.346A>C	p.Asn116His	missense_variant, splice_region_variant	7/8	3

Frequencies

GnomAD3 genomes

AF:

0.00000905

AC:

AN:

110501

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32751

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000971

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:

0.0000224

AC:

AN:

178566

Hom.:

AF XY:

0.0000316

AC XY:

AN XY:

63242

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000113

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:

0.0000125

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1091974

Hom.:

Cov.:

AF XY:

0.00000839

AC XY:

AN XY:

357674

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000114

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:

0.00000119

Gnomad4 OTH exome

AF:

0.0000218

GnomAD4 genome

AF:

0.00000905

AC:

AN:

110501

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32751

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000971

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

Bravo

AF:

0.0000793

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.99

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.72

T;T;T;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.087

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.46

REVEL

Benign

0.021

Polyphen

1.0

.;.;D;D

Vest4

0.25

MutPred

0.21

.;.;Gain of catalytic residue at N138 (P = 0.0425);.;

MVP

0.24

MPC

0.53

ClinPred

0.23

GERP RS

2.4

Varity_R

0.13

gMVP

0.14

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over