NM_001141919.2:c.220C>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001141919.2(XG):​c.220C>T​(p.Gln74*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000957 in 1,044,898 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.6e-7 (0 hom. 0 hem.)
• Consequence: XG NM_001141919.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>T	p.Gln74*	stop_gained	Exon 5 of 11	NP_001135391.1	P55808-3
	XG	NM_001141920.2		c.220C>T	p.Gln74*	stop_gained	Exon 5 of 10	NP_001135392.1	P55808-2
	XG	NM_175569.3		c.220C>T	p.Gln74*	stop_gained	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>T	p.Gln74*	stop_gained	Exon 5 of 11	ENSP00000494087.1	P55808-3
	XG	ENST00000381174.10	TSL:1	c.220C>T	p.Gln74*	stop_gained	Exon 5 of 10	ENSP00000370566.5	P55808-1
	XG	ENST00000419513.7	TSL:1	c.154C>T	p.Gln52*	stop_gained	Exon 3 of 9	ENSP00000411004.3	A0A2U3U020

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000789 AC: 1 AN: 126775 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000183

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.57e-7 AC: 1 AN: 1044898 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 329448

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: 45110

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: 814522

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

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	33
DANN	Benign	0.96
FATHMM_MKL	Benign	0.0090	N
PhyloP100		0.39
Vest4		0.88
GERP RS		0.37
Mutation Taster		=169/31	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;