X-2782081-C-T

Variant names:

• chrX-2782081-C-T
• rs376745839
• NM_001141919.2:c.143C>T

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.143C>T​(p.Pro48Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 1,209,882 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000019 (0 hom. 9 hem.)
• Consequence: XG NM_001141919.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54
• 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=0.11434412).
• BS2: High Hemizygotes in GnomAdExome4 at 9 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.143C>T	p.Pro48Leu	missense	Exon 4 of 11	NP_001135391.1	P55808-3
	XG	NM_001141920.2		c.143C>T	p.Pro48Leu	missense	Exon 4 of 10	NP_001135392.1	P55808-2
	XG	NM_175569.3		c.143C>T	p.Pro48Leu	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.143C>T	p.Pro48Leu	missense	Exon 4 of 11	ENSP00000494087.1	P55808-3
	XG	ENST00000381174.10	TSL:1	c.143C>T	p.Pro48Leu	missense	Exon 4 of 10	ENSP00000370566.5	P55808-1
	XG	ENST00000419513.7	TSL:1	c.77C>T	p.Pro26Leu	missense	Exon 2 of 9	ENSP00000411004.3	A0A2U3U020

Frequencies

GnomAD3 genomes AF: 0.0000447 AC: 5 AN: 111897 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000163

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000436 AC: 8 AN: 183431 AF XY: 0.0000442

Gnomad AFR exome AF: 0.000304

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.000134

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000244

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000191 AC: 21 AN: 1097985 Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 9 AN XY: 363349

African (AFR) AF: 0.000189 AC: 5 AN: 26399

American (AMR) AF: 0.0000568 AC: 2 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.0000516 AC: 1 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30176

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54115

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.00000950 AC: 8 AN: 841949

Other (OTH) AF: 0.0000868 AC: 4 AN: 46090

GnomAD4 genome AF: 0.0000447 AC: 5 AN: 111897 Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1 AN XY: 34069

African (AFR) AF: 0.000163 AC: 5 AN: 30737

American (AMR) AF: 0.00 AC: 0 AN: 10500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3571

South Asian (SAS) AF: 0.00 AC: 0 AN: 2680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6115

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53216

Other (OTH) AF: 0.00 AC: 0 AN: 1502

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000494 AC: 6

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	0.16
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.5
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.048
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.39
MVP		0.040
MPC		0.53
ClinPred		0.35	T
GERP RS		1.2
Varity_R		0.33
gMVP		0.13
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs376745839; hg19: chrX-2700122;