X-2789703-G-A

Variant names:

• chrX-2789703-G-A
• rs374318565
• NM_001141919.2:c.250G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001141919.2(XG):​c.250G>A​(p.Gly84Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,084,096 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 41 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G84G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000064 (0 hom., 3 hem., cov: 23)
  • Exomes 𝑓: 0.00014 (0 hom. 38 hem.)
• Consequence: XG NM_001141919.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20305276).
• BS2: High Hemizygotes in GnomAd4 at 3 BG gene

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.250G>A	p.Gly84Arg	missense	Exon 5 of 11	NP_001135391.1	P55808-3
	XG	NM_001141920.2		c.250G>A	p.Gly84Arg	missense	Exon 5 of 10	NP_001135392.1	P55808-2
	XG	NM_175569.3		c.250G>A	p.Gly84Arg	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.250G>A	p.Gly84Arg	missense	Exon 5 of 11	ENSP00000494087.1	P55808-3
	XG	ENST00000381174.10	TSL:1	c.250G>A	p.Gly84Arg	missense	Exon 5 of 10	ENSP00000370566.5	P55808-1
	XG	ENST00000419513.7	TSL:1	c.184G>A	p.Gly62Arg	missense	Exon 3 of 9	ENSP00000411004.3	A0A2U3U020

Frequencies

GnomAD3 genomes AF: 0.0000635 AC: 7 AN: 110156 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000296 AC: 3 AN: 101478 AF XY: 0.0000402

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: 0.0000697

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000140 AC: 136 AN: 973940 Hom.: 0 Cov.: 20 AF XY: 0.000136 AC XY: 38 AN XY: 279478

African (AFR) AF: 0.00 AC: 0 AN: 22337

American (AMR) AF: 0.00 AC: 0 AN: 24080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17199

East Asian (EAS) AF: 0.00 AC: 0 AN: 25263

South Asian (SAS) AF: 0.00 AC: 0 AN: 36655

European-Finnish (FIN) AF: 0.0000825 AC: 3 AN: 36379

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3818

European-Non Finnish (NFE) AF: 0.000169 AC: 130 AN: 767175

Other (OTH) AF: 0.0000731 AC: 3 AN: 41034

GnomAD4 genome AF: 0.0000635 AC: 7 AN: 110156 Hom.: 0 Cov.: 23 AF XY: 0.0000912 AC XY: 3 AN XY: 32912

African (AFR) AF: 0.00 AC: 0 AN: 29901

American (AMR) AF: 0.00 AC: 0 AN: 10426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2634

East Asian (EAS) AF: 0.00 AC: 0 AN: 3577

South Asian (SAS) AF: 0.00 AC: 0 AN: 2617

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5724

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 233

European-Non Finnish (NFE) AF: 0.000132 AC: 7 AN: 52859

Other (OTH) AF: 0.00 AC: 0 AN: 1499

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000718

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.0000463 AC: 5

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	0.33
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.21	T
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.59	T
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.7
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.12
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.99	D
Vest4		0.39
MutPred		0.15		Gain of methylation at G84 (P = 0.0314)
MVP		0.095
MPC		0.20
ClinPred		0.62	D
GERP RS		2.3
Varity_R		0.22
gMVP		0.11
Mutation Taster		=98/2	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: rs374318565; hg19: chrX-2707744;