Variant X-2782104-C-G 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.166C>G(p.Pro56Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,210,211 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 37 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 0.00012 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00012 ( 0 hom. 31 hem. )

Consequence

XG
NM_001141919.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

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=0.069767594).

BS2

High Hemizygotes in GnomAd4 at 6 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XG	NM_001141919.2 linkuse as main transcript	c.166C>G	p.Pro56Ala	missense_variant	4/11	ENST00000644266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XG	ENST00000644266.2 linkuse as main transcript	c.166C>G	p.Pro56Ala	missense_variant	4/11		NM_001141919.2		P55808-3
XG	ENST00000381174.10 linkuse as main transcript	c.166C>G	p.Pro56Ala	missense_variant	4/10	1		P1	P55808-1
XG	ENST00000419513.7 linkuse as main transcript	c.100C>G	p.Pro34Ala	missense_variant	2/9	1
XG	ENST00000509484.3 linkuse as main transcript	c.100C>G	p.Pro34Ala	missense_variant	2/8	3

Frequencies

GnomAD3 genomes

AF:

0.000116

AC:

AN:

112258

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

34400

show subpopulations

Gnomad AFR

AF:

0.0000324

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:

0.000325

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000654

AC:

AN:

183442

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

67874

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:

0.000250

Gnomad NFE exome

AF:

0.0000855

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000116

AC:

127

AN:

1097953

Hom.:

Cov.:

AF XY:

0.0000853

AC XY:

AN XY:

363313

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:

0.000271

Gnomad4 NFE exome

AF:

0.000133

Gnomad4 OTH exome

AF:

0.0000868

GnomAD4 genome

AF:

0.000116

AC:

AN:

112258

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

34400

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000325

Gnomad4 NFE

AF:

0.000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000741

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

Jun 22, 2021

The c.166C>G (p.P56A) alteration is located in exon 4 (coding exon 4) of the XG gene. This alteration results from a C to G substitution at nucleotide position 166, causing the proline (P) at amino acid position 56 to be replaced by an alanine (A). 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

0.099

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.5

DANN

Benign

0.96

DEOGEN2

Benign

0.20

.;.;T;.

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.57

T;T;T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.070

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

.;.;M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-4.3

D;N;D;.

REVEL

Benign

0.070

Sift

Pathogenic

0.0

D;T;T;.

Sift4G

Benign

0.19

.;T;T;.

Polyphen

1.0, 0.81

.;.;D;P

Vest4

0.44

MutPred

0.15

.;.;Loss of glycosylation at P56 (P = 0.0408);Loss of glycosylation at P56 (P = 0.0408);

MVP

0.014

MPC

0.48

ClinPred

0.41

GERP RS

1.2

Varity_R

0.10

gMVP

0.074

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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