Variant X-73842826-A-G 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.9928T>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 0.0154 in 556,416 control chromosomes in the GnomAD database, including 388 homozygotes. There are 2,547 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 ( 265 hom., 1328 hem., cov: 22)

Exomes 𝑓: 0.0083 ( 123 hom. 1219 hem. )

Consequence

XIST
NR_001564.2 non_coding_transcript_exon

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.240

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=-0.9).

BP6

Variant X-73842826-A-G is Benign according to our data. Variant chrX-73842826-A-G is described in ClinVar as [Benign]. Clinvar id is 3039258.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.9928T>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.9898T>C		non_coding_transcript_exon_variant	1/6	1

Frequencies

GnomAD3 genomes

AF:

0.0437

AC:

4857

AN:

111038

Hom.:

265

Cov.:

AF XY:

0.0400

AC XY:

1330

AN XY:

33254

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0200

Gnomad ASJ

AF:

0.00872

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00756

Gnomad FIN

AF:

0.000833

Gnomad MID

AF:

0.00424

Gnomad NFE

AF:

0.00126

Gnomad OTH

AF:

0.0340

GnomAD3 exomes

AF:

0.0140

AC:

2347

AN:

167319

Hom.:

112

AF XY:

0.0117

AC XY:

741

AN XY:

63553

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.0103

Gnomad ASJ exome

AF:

0.00932

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00616

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.00157

Gnomad OTH exome

AF:

0.00813

GnomAD4 exome

AF:

0.00834

AC:

3715

AN:

445324

Hom.:

123

Cov.:

AF XY:

0.00728

AC XY:

1219

AN XY:

167424

show subpopulations

Gnomad4 AFR exome

AF:

0.153

Gnomad4 AMR exome

AF:

0.0110

Gnomad4 ASJ exome

AF:

0.00831

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00646

Gnomad4 FIN exome

AF:

0.000808

Gnomad4 NFE exome

AF:

0.00151

Gnomad4 OTH exome

AF:

0.0145

GnomAD4 genome

AF:

0.0437

AC:

4855

AN:

111092

Hom.:

265

Cov.:

AF XY:

0.0399

AC XY:

1328

AN XY:

33318

show subpopulations

Gnomad4 AFR

AF:

0.147

Gnomad4 AMR

AF:

0.0200

Gnomad4 ASJ

AF:

0.00872

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00758

Gnomad4 FIN

AF:

0.000833

Gnomad4 NFE

AF:

0.00126

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0173

Hom.:

174

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

-0.90

CADD

Benign

1.8

DANN

Benign

0.37

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