rs749989792

Variant names:

• chrX-2811338-A-C
• rs749989792
• NM_001141919.2:c.457A>C

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.457A>C​(p.Asn153His) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000582 in 1,202,475 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.0000055 (0 hom. 3 hem.)
• Consequence: XG NM_001141919.2 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.676
• 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]

ENSG00000305418 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.087411135).
• BS2: High Hemizygotes in GnomAdExome4 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.457A>C	p.Asn153His	missense splice_region	Exon 10 of 11	NP_001135391.1	P55808-3
	XG	NM_001141920.2		c.415A>C	p.Asn139His	missense splice_region	Exon 9 of 10	NP_001135392.1	P55808-2
	XG	NM_175569.3		c.412A>C	p.Asn138His	missense splice_region	Exon 9 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.457A>C	p.Asn153His	missense splice_region	Exon 10 of 11	ENSP00000494087.1	P55808-3
	XG	ENST00000381174.10	TSL:1	c.412A>C	p.Asn138His	missense splice_region	Exon 9 of 10	ENSP00000370566.5	P55808-1
	XG	ENST00000419513.7	TSL:1	c.391A>C	p.Asn131His	missense splice_region	Exon 8 of 9	ENSP00000411004.3	A0A2U3U020

Frequencies

GnomAD3 genomes AF: 0.00000905 AC: 1 AN: 110501 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000971

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000224 AC: 4 AN: 178566 AF XY: 0.0000316

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000113

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000125

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000549 AC: 6 AN: 1091974 Hom.: 0 Cov.: 28 AF XY: 0.00000839 AC XY: 3 AN XY: 357674

African (AFR) AF: 0.00 AC: 0 AN: 26315

American (AMR) AF: 0.000114 AC: 4 AN: 34960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19265

East Asian (EAS) AF: 0.00 AC: 0 AN: 30124

South Asian (SAS) AF: 0.00 AC: 0 AN: 53015

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4102

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 838002

Other (OTH) AF: 0.0000218 AC: 1 AN: 45823

GnomAD4 genome AF: 0.00000905 AC: 1 AN: 110501 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 32751

African (AFR) AF: 0.00 AC: 0 AN: 30324

American (AMR) AF: 0.0000971 AC: 1 AN: 10301

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2631

East Asian (EAS) AF: 0.00 AC: 0 AN: 3526

South Asian (SAS) AF: 0.00 AC: 0 AN: 2548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5848

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52921

Other (OTH) AF: 0.00 AC: 0 AN: 1487

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000793

ExAC AF: 0.00000824 AC: 1

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	0.30
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.68
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.021
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.027	D
Polyphen		1.0	D
Vest4		0.25
MutPred		0.21		Gain of catalytic residue at N138 (P = 0.0425)
MVP		0.24
MPC		0.53
ClinPred		0.23	T
GERP RS		2.4
Varity_R		0.13
gMVP		0.14
Mutation Taster		=94/6	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: rs749989792; hg19: chrX-2729379;