X-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

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: 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 id is 769483.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-2811333-C-T is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAd4 at 75 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XG	NM_001141919.2	c.455-3C>T		splice_region_variant, intron_variant	Intron 9 of 10	ENST00000644266.2	NP_001135391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XG	ENST00000644266.2	c.455-3C>T		splice_region_variant, intron_variant	Intron 9 of 10		NM_001141919.2	ENSP00000494087.1
XG	ENST00000381174.10	c.410-3C>T		splice_region_variant, intron_variant	Intron 8 of 9	1		ENSP00000370566.5
XG	ENST00000419513.7	c.389-3C>T		splice_region_variant, intron_variant	Intron 7 of 8	1		ENSP00000411004.3
XG	ENST00000509484.3	c.344-3C>T		splice_region_variant, intron_variant	Intron 6 of 7	3		ENSP00000430005.2

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

Gnomad4 AFR exome AF: 0.000344 AC: 9 AN: 26194

Gnomad4 AMR exome AF: 0.00116 AC: 40 AN: 34624

Gnomad4 ASJ exome AF: 0.000993 AC: 19 AN: 19137

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 30065

Gnomad4 SAS exome AF: 0.000518 AC: 27 AN: 52169

Gnomad4 FIN exome AF: 0.00109 AC: 44 AN: 40302

Gnomad4 NFE exome AF: 0.00439 AC: 3658 AN: 833853

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.000460 AC: 0.00045968 AN: 0.00045968

Gnomad4 AMR AF: 0.00155 AC: 0.00154784 AN: 0.00154784

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000392 AC: 0.000392157 AN: 0.000392157

Gnomad4 FIN AF: 0.00102 AC: 0.00102249 AN: 0.00102249

Gnomad4 NFE AF: 0.00453 AC: 0.00453035 AN: 0.00453035

Gnomad4 OTH AF: 0.00333 AC: 0.00332889 AN: 0.00332889

Alfa AF: 0.00290 Hom.: 28

Bravo AF: 0.00233

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:3

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 19, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.2
DANN	Benign	0.62
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

Publications

LitVar

Other links and lift over

dbSNP: rs202025841; hg19: chrX-2729374;