Variant X-73842633-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NR_001564.2(XIST):n.10121A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 556,299 control chromosomes in the GnomAD database, including 390 homozygotes. There are 2,559 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.044 ( 267 hom., 1344 hem., cov: 22)

Exomes 𝑓: 0.0083 ( 123 hom. 1215 hem. )

Consequence

XIST
NR_001564.2 non_coding_transcript_exon

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.280

Variant links:

Genes affected

XIST (HGNC:12810): (X inactive specific transcript) X inactivation is an early developmental process in mammalian females that transcriptionally silences one of the pair of X chromosomes, thus providing dosage equivalence between males and females. The process is regulated by several factors, including a region of chromosome X called the X inactivation center (XIC). The XIC comprises several non-coding and protein-coding genes, and this gene was the first non-coding gene identified within the XIC. This gene is expressed exclusively from the XIC of the inactive X chromosome, and is essential for the initiation and spread of X-inactivation. The transcript is a spliced RNA. Alternatively spliced transcript variants have been identified, but their full length sequences have not been determined. Mutations in the XIST promoter cause familial skewed X inactivation. [provided by RefSeq, Apr 2012]

XIST links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-73842633-T-C is Benign according to our data. Variant chrX-73842633-T-C is described in ClinVar as [Benign]. Clinvar id is 3038835.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIST	NR_001564.2 linkuse as main transcript	n.10121A>G		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XIST	ENST00000429829.6 linkuse as main transcript	n.10091A>G		non_coding_transcript_exon_variant	1/6	1

Frequencies

GnomAD3 genomes

AF:

0.0439

AC:

4877

AN:

111090

Hom.:

267

Cov.:

AF XY:

0.0404

AC XY:

1346

AN XY:

33308

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0196

Gnomad ASJ

AF:

0.00870

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00797

Gnomad FIN

AF:

0.000670

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00124

Gnomad OTH

AF:

0.0368

GnomAD3 exomes

AF:

0.0140

AC:

2338

AN:

166774

Hom.:

112

AF XY:

0.0116

AC XY:

730

AN XY:

62974

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.0102

Gnomad ASJ exome

AF:

0.00933

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00612

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.00155

Gnomad OTH exome

AF:

0.00839

GnomAD4 exome

AF:

0.00834

AC:

3712

AN:

445156

Hom.:

123

Cov.:

AF XY:

0.00726

AC XY:

1215

AN XY:

167262

show subpopulations

Gnomad4 AFR exome

AF:

0.153

Gnomad4 AMR exome

AF:

0.0109

Gnomad4 ASJ exome

AF:

0.00831

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00649

Gnomad4 FIN exome

AF:

0.000808

Gnomad4 NFE exome

AF:

0.00151

Gnomad4 OTH exome

AF:

0.0145

GnomAD4 genome

AF:

0.0439

AC:

4875

AN:

111143

Hom.:

267

Cov.:

AF XY:

0.0403

AC XY:

1344

AN XY:

33371

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.0195

Gnomad4 ASJ

AF:

0.00870

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00800

Gnomad4 FIN

AF:

0.000670

Gnomad4 NFE

AF:

0.00124

Gnomad4 OTH

AF:

0.0363

Alfa

AF:

0.00690

Hom.:

Bravo

AF:

0.0509

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

XIST-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 20, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.2

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

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