Variant X-2811333-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001141919.2(XG):c.455-3C>T variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.02106

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 2.28

Variant links:

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]

XG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
XG	NM_001141919.2 linkuse as main transcript	c.455-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000644266.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
XG	ENST00000644266.2 linkuse as main transcript	c.455-3C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NM_001141919.2		P55808-3
XG	ENST00000381174.10 linkuse as main transcript	c.410-3C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		P1	P55808-1
XG	ENST00000419513.7 linkuse as main transcript	c.389-3C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1
XG	ENST00000509484.3 linkuse as main transcript	c.344-3C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00255

AC:

282

AN:

110693

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

AN XY:

32899

show subpopulations

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

GnomAD3 exomes

AF:

0.00248

AC:

439

AN:

176779

Hom.:

AF XY:

0.00239

AC XY:

147

AN XY:

61589

show subpopulations

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 SAS exome

AF:

0.000403

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.:

Cov.:

AF XY:

0.00360

AC XY:

1267

AN XY:

352387

show subpopulations

Gnomad4 AFR exome

AF:

0.000344

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.000993

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000518

Gnomad4 FIN exome

AF:

0.00109

Gnomad4 NFE exome

AF:

0.00439

Gnomad4 OTH exome

AF:

0.00338

GnomAD4 genome

AF:

0.00255

AC:

282

AN:

110743

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

AN XY:

32959

show subpopulations

Gnomad4 AFR

AF:

0.000460

Gnomad4 AMR

AF:

0.00155

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000392

Gnomad4 FIN

AF:

0.00102

Gnomad4 NFE

AF:

0.00453

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.00290

Hom.:

Bravo

AF:

0.00233

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 19, 2018	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.2

DANN

Benign

0.62

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over