NM_001141919.2:c.220C>G

Variant names:

• chrX-2789673-C-G
• rs1421632593
• NM_001141919.2:c.220C>G

Variant summary

Our verdict is Likely benign. The variant received -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. 15/21 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059029102).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001141919.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XG	NM_001141919.2	MANE Select	c.220C>G	p.Gln74Glu	missense	Exon 5 of 11	NP_001135391.1	P55808-3
	XG	NM_001141920.2		c.220C>G	p.Gln74Glu	missense	Exon 5 of 10	NP_001135392.1	P55808-2
	XG	NM_175569.3		c.220C>G	p.Gln74Glu	missense	Exon 5 of 10	NP_780778.1	P55808-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XG	ENST00000644266.2	MANE Select	c.220C>G	p.Gln74Glu	missense	Exon 5 of 11	ENSP00000494087.1	P55808-3
	XG	ENST00000381174.10	TSL:1	c.220C>G	p.Gln74Glu	missense	Exon 5 of 10	ENSP00000370566.5	P55808-1
	XG	ENST00000419513.7	TSL:1	c.154C>G	p.Gln52Glu	missense	Exon 3 of 9	ENSP00000411004.3	A0A2U3U020

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

African (AFR) AF: 0.00 AC: 0 AN: 24462

American (AMR) AF: 0.00 AC: 0 AN: 28962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18364

East Asian (EAS) AF: 0.00 AC: 0 AN: 27363

South Asian (SAS) AF: 0.00 AC: 0 AN: 45112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38323

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4012

European-Non Finnish (NFE) AF: 0.00000123 AC: 1 AN: 814521

Other (OTH) AF: 0.00 AC: 0 AN: 43780

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.39
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.040
Sift	Benign	0.22	T
Sift4G	Benign	1.0	T
Polyphen		0.011	B
Vest4		0.15
MutPred		0.10		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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1421632593; hg19: chrX-2707714;