Variant X-2789673-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001141919.2(XG):c.220C>G(p.Gln74Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000957 in 1,044,899 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.6e-7 ( 0 hom. 1 hem. )

Consequence

XG
NM_001141919.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.385

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059029102).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XG	NM_001141919.2 linkuse as main transcript	c.220C>G	p.Gln74Glu	missense_variant	5/11	ENST00000644266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XG	ENST00000644266.2 linkuse as main transcript	c.220C>G	p.Gln74Glu	missense_variant	5/11		NM_001141919.2		P55808-3
XG	ENST00000381174.10 linkuse as main transcript	c.220C>G	p.Gln74Glu	missense_variant	5/10	1		P1	P55808-1
XG	ENST00000419513.7 linkuse as main transcript	c.154C>G	p.Gln52Glu	missense_variant	3/9	1
XG	ENST00000509484.3 linkuse as main transcript	c.154C>G	p.Gln52Glu	missense_variant	3/8	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.57e-7

AC:

AN:

1044899

Hom.:

Cov.:

AF XY:

0.00000304

AC XY:

AN XY:

329449

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:

0.00000123

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 13, 2022

The c.220C>G (p.Q74E) alteration is located in exon 5 (coding exon 5) of the XG gene. This alteration results from a C to G substitution at nucleotide position 220, causing the glutamine (Q) at amino acid position 74 to be replaced by a glutamic acid (E). 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

-0.90

CADD

Benign

0.66

DANN

Benign

0.23

DEOGEN2

Benign

0.097

.;.;T;.

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.63

T;T;T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.059

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

.;.;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.5

.;N;N;.

REVEL

Benign

0.040

Sift

Benign

0.22

.;T;T;.

Sift4G

Benign

1.0

.;T;T;.

Polyphen

0.011, 0.0090

.;.;B;B

Vest4

0.15

MutPred

0.10

.;.;Gain of ubiquitination at K70 (P = 0.0566);Gain of ubiquitination at K70 (P = 0.0566);

MVP

0.014

MPC

0.12

ClinPred

0.11

GERP RS

0.37

Varity_R

0.13

gMVP

0.035

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over