Variant X-73842183-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NR_001564.2(XIST):n.10571T>C 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 0.00123 in 509,228 control chromosomes in the GnomAD database, including 4 homozygotes. There are 171 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., 119 hem., cov: 23)

Exomes 𝑓: 0.00054 ( 1 hom. 52 hem. )

Consequence

XIST
NR_001564.2 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.758

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant X-73842183-A-G is Benign according to our data. Variant chrX-73842183-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3040534.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIST	NR_001564.2 linkuse as main transcript	n.10571T>C		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.10541T>C		non_coding_transcript_exon_variant	1/6	1

Frequencies

GnomAD3 genomes

AF:

0.00365

AC:

408

AN:

111731

Hom.:

Cov.:

AF XY:

0.00348

AC XY:

118

AN XY:

33903

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000478

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.0000752

Gnomad OTH

AF:

0.00200

GnomAD3 exomes

AF:

0.00107

AC:

104

AN:

97329

Hom.:

AF XY:

0.000670

AC XY:

AN XY:

34311

show subpopulations

Gnomad AFR exome

AF:

0.0182

Gnomad AMR exome

AF:

0.000533

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000543

AC:

216

AN:

397445

Hom.:

Cov.:

AF XY:

0.000355

AC XY:

AN XY:

146365

show subpopulations

Gnomad4 AFR exome

AF:

0.0148

Gnomad4 AMR exome

AF:

0.000376

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:

0.0000215

Gnomad4 OTH exome

AF:

0.000786

GnomAD4 genome

AF:

0.00366

AC:

409

AN:

111783

Hom.:

Cov.:

AF XY:

0.00350

AC XY:

119

AN XY:

33965

show subpopulations

Gnomad4 AFR

AF:

0.0129

Gnomad4 AMR

AF:

0.000477

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000752

Gnomad4 OTH

AF:

0.00197

Alfa

AF:

0.00227

Hom.:

Bravo

AF:

0.00425

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

XIST-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 20, 2019

This variant is classified as likely 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

-0.90

CADD

Benign

4.2

DANN

Benign

0.18

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