NM_001141919.2:c.166C>G

Variant names:

• chrX-2782104-C-G
• rs761656749
• NM_001141919.2:c.166C>G

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.166C>G​(p.Pro56Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,210,211 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 37 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., 6 hem., cov: 23)
  • Exomes 𝑓: 0.00012 (0 hom. 31 hem.)
• Consequence: XG NM_001141919.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.60
• 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=0.069767594).
• BS2: High Hemizygotes in GnomAd4 at 6 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.166C>G	p.Pro56Ala	missense	Exon 4 of 11	NP_001135391.1	P55808-3
	XG	NM_001141920.2		c.166C>G	p.Pro56Ala	missense	Exon 4 of 10	NP_001135392.1	P55808-2
	XG	NM_175569.3		c.166C>G	p.Pro56Ala	missense	Exon 4 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.166C>G	p.Pro56Ala	missense	Exon 4 of 11	ENSP00000494087.1	P55808-3
	XG	ENST00000381174.10	TSL:1	c.166C>G	p.Pro56Ala	missense	Exon 4 of 10	ENSP00000370566.5	P55808-1
	XG	ENST00000419513.7	TSL:1	c.100C>G	p.Pro34Ala	missense	Exon 2 of 9	ENSP00000411004.3	A0A2U3U020

Frequencies

GnomAD3 genomes AF: 0.000116 AC: 13 AN: 112258 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000324

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: 0.000325

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000654 AC: 12 AN: 183442 AF XY: 0.0000589

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: 0.000250

Gnomad NFE exome AF: 0.0000855

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.000116 AC: 127 AN: 1097953 Hom.: 0 Cov.: 30 AF XY: 0.0000853 AC XY: 31 AN XY: 363313

African (AFR) AF: 0.00 AC: 0 AN: 26400

American (AMR) AF: 0.00 AC: 0 AN: 35203

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30175

South Asian (SAS) AF: 0.00 AC: 0 AN: 54118

European-Finnish (FIN) AF: 0.000271 AC: 11 AN: 40531

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.000133 AC: 112 AN: 841916

Other (OTH) AF: 0.0000868 AC: 4 AN: 46087

GnomAD4 genome AF: 0.000116 AC: 13 AN: 112258 Hom.: 0 Cov.: 23 AF XY: 0.000174 AC XY: 6 AN XY: 34400

African (AFR) AF: 0.0000324 AC: 1 AN: 30856

American (AMR) AF: 0.00 AC: 0 AN: 10565

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3586

South Asian (SAS) AF: 0.00 AC: 0 AN: 2692

European-Finnish (FIN) AF: 0.000325 AC: 2 AN: 6145

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.000188 AC: 10 AN: 53324

Other (OTH) AF: 0.00 AC: 0 AN: 1513

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.000109

EpiControl AF: 0.000119

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	-0.68
CADD	Benign	7.5
DANN	Benign	0.96
DEOGEN2	Benign	0.20	T
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.6
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.070
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.19	T
Polyphen		1.0	D
Vest4		0.44
MutPred		0.15		Loss of glycosylation at P56 (P = 0.0408)
MVP		0.014
MPC		0.48
ClinPred		0.41	T
GERP RS		1.2
Varity_R		0.10
gMVP		0.074
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs761656749; hg19: chrX-2700145;