X-2789673-C-G

Variant names:

• chrX-2789673-C-G
• NM_001141919.2:c.220C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.385

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]

ACMG classification

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 rank	MANE	Protein	UniProt
XG	NM_001141919.2	c.220C>G	p.Gln74Glu	missense_variant	Exon 5 of 11	ENST00000644266.2	NP_001135391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XG	ENST00000644266.2	c.220C>G	p.Gln74Glu	missense_variant	Exon 5 of 11		NM_001141919.2	ENSP00000494087.1
XG	ENST00000381174.10	c.220C>G	p.Gln74Glu	missense_variant	Exon 5 of 10	1		ENSP00000370566.5
XG	ENST00000419513.7	c.154C>G	p.Gln52Glu	missense_variant	Exon 3 of 9	1		ENSP00000411004.3
XG	ENST00000509484.3	c.154C>G	p.Gln52Glu	missense_variant	Exon 3 of 8	3		ENSP00000430005.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.57e-7 AC: 1 AN: 1044899 Hom.: 0 Cov.: 25 AF XY: 0.00000304 AC XY: 1 AN XY: 329449

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.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 13, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.66
DANN	Benign	0.23
DEOGEN2	Benign	0.097	.;.;T;.
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.63	T;T;T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.059	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	.;.;N;N
PrimateAI	Benign	0.30	T
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	T
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.

Other links and lift over

hg19: chrX-2707714;