X-2797355-C-T

Variant names:

• chrX-2797355-C-T
• rs753335679
• NM_001141919.2:c.368C>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001141919.2(XG):​c.368C>T​(p.Thr123Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000729 in 1,097,169 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000073 (0 hom. 3 hem.)
• Consequence: XG NM_001141919.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14933276).
• BS2: High Hemizygotes in GnomAdExome4 at 3 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XG	NM_001141919.2	c.368C>T	p.Thr123Met	missense_variant	Exon 7 of 11	ENST00000644266.2	NP_001135391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XG	ENST00000644266.2	c.368C>T	p.Thr123Met	missense_variant	Exon 7 of 11		NM_001141919.2	ENSP00000494087.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000729 AC: 8 AN: 1097169 Hom.: 0 Cov.: 30 AF XY: 0.00000827 AC XY: 3 AN XY: 362557

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000951

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

Alfa AF: 0.0000680 Hom.: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	.;.;T;.
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.53	T;T;T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	.;.;M;M
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.2	.;D;N;.
REVEL	Benign	0.12
Sift	Pathogenic	0.0	.;D;D;.
Sift4G	Uncertain	0.021	.;D;T;.
Polyphen		1.0	.;.;D;D
Vest4		0.34
MutPred		0.092		.;.;Loss of glycosylation at T123 (P = 0.01);Loss of glycosylation at T123 (P = 0.01);
MVP		0.048
MPC		0.23
ClinPred		0.65	D
GERP RS		1.4
Varity_R		0.15
gMVP		0.12

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

Publications

LitVar

Other links and lift over

dbSNP: rs753335679; hg19: chrX-2715396; COSMIC: COSV66985843;