chrX-2811333-C-T

Variant names:

• chrX-2811333-C-T
• rs202025841
• NM_001141919.2:c.455-3C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001141919.2(XG):​c.455-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,196,774 control chromosomes in the GnomAD database, including 5 homozygotes. There are 1,342 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., 75 hem., cov: 22)
  • Exomes 𝑓: 0.0036 (5 hom. 1267 hem.)
• Consequence: XG NM_001141919.2 splice_region, intron
• Scores: Splicing: ADA: 0.02106
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 2.28
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant X-2811333-C-T is Benign according to our data. Variant chrX-2811333-C-T is described in ClinVar as Benign. ClinVar VariationId is 769483.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 75 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.455-3C>T		splice_region intron	N/A	NP_001135391.1	P55808-3
	XG	NM_001141920.2		c.413-3C>T		splice_region intron	N/A	NP_001135392.1	P55808-2
	XG	NM_175569.3		c.410-3C>T		splice_region intron	N/A	NP_780778.1	P55808-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XG	ENST00000644266.2	MANE Select	c.455-3C>T		splice_region intron	N/A	ENSP00000494087.1	P55808-3
	XG	ENST00000381174.10	TSL:1	c.410-3C>T		splice_region intron	N/A	ENSP00000370566.5	P55808-1
	XG	ENST00000419513.7	TSL:1	c.389-3C>T		splice_region intron	N/A	ENSP00000411004.3	A0A2U3U020

Frequencies

GnomAD3 genomes AF: 0.00255 AC: 282 AN: 110693 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000461

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00155

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000391

Gnomad FIN AF: 0.00102

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00453

Gnomad OTH AF: 0.00337

GnomAD2 exomes AF: 0.00248 AC: 439 AN: 176779 AF XY: 0.00239

Gnomad AFR exome AF: 0.000309

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.000690

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00101

Gnomad NFE exome AF: 0.00466

Gnomad OTH exome AF: 0.00207

GnomAD4 exome AF: 0.00364 AC: 3952 AN: 1086031 Hom.: 5 Cov.: 28 AF XY: 0.00360 AC XY: 1267 AN XY: 352387

African (AFR) AF: 0.000344 AC: 9 AN: 26194

American (AMR) AF: 0.00116 AC: 40 AN: 34624

Ashkenazi Jewish (ASJ) AF: 0.000993 AC: 19 AN: 19137

East Asian (EAS) AF: 0.00 AC: 0 AN: 30065

South Asian (SAS) AF: 0.000518 AC: 27 AN: 52169

European-Finnish (FIN) AF: 0.00109 AC: 44 AN: 40302

Middle Eastern (MID) AF: 0.000246 AC: 1 AN: 4070

European-Non Finnish (NFE) AF: 0.00439 AC: 3658 AN: 833853

Other (OTH) AF: 0.00338 AC: 154 AN: 45617

GnomAD4 genome AF: 0.00255 AC: 282 AN: 110743 Hom.: 0 Cov.: 22 AF XY: 0.00228 AC XY: 75 AN XY: 32959

African (AFR) AF: 0.000460 AC: 14 AN: 30456

American (AMR) AF: 0.00155 AC: 16 AN: 10337

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2638

East Asian (EAS) AF: 0.00 AC: 0 AN: 3522

South Asian (SAS) AF: 0.000392 AC: 1 AN: 2550

European-Finnish (FIN) AF: 0.00102 AC: 6 AN: 5868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00453 AC: 240 AN: 52976

Other (OTH) AF: 0.00333 AC: 5 AN: 1502

Alfa AF: 0.00290 Hom.: 28

Bravo AF: 0.00233

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.2
DANN	Benign	0.62
PhyloP100		2.3
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.021
dbscSNV1_RF	Benign	0.24
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: rs202025841; hg19: chrX-2729374;