Variant chrX-73824521-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NR_001564.2(XIST):n.15410C>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 0.00179 in 554,741 control chromosomes in the GnomAD database, including 2 homozygotes. There are 412 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 0.0012 ( 0 hom., 44 hem., cov: 23)

Exomes 𝑓: 0.0019 ( 2 hom. 368 hem. )

Consequence

XIST
NR_001564.2 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.28

Variant links:

Genes affected

XIST (HGNC:):

XIST links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant X-73824521-G-C is Benign according to our data. Variant chrX-73824521-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3350445.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00194 (860/442609) while in subpopulation MID AF= 0.0265 (79/2985). AF 95% confidence interval is 0.0218. There are 2 homozygotes in gnomad4_exome. There are 368 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 44 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIST	NR_001564.2 linkuse as main transcript	n.15410C>G		non_coding_transcript_exon_variant	6/6
TSIX	NR_003255.2 linkuse as main transcript	n.32317G>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL
XIST	ENST00000429829.6 linkuse as main transcript	n.15380C>G	non_coding_transcript_exon_variant	6/6	1
TSIX	ENST00000604411.1 linkuse as main transcript	n.32317G>C	non_coding_transcript_exon_variant	1/1	6
XIST	ENST00000648970.1 linkuse as main transcript	n.5344C>G	non_coding_transcript_exon_variant	7/7

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

134

AN:

112080

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

34258

show subpopulations

Gnomad AFR

AF:

0.0000972

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00254

Gnomad ASJ

AF:

0.00454

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00291

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0168

Gnomad NFE

AF:

0.00136

Gnomad OTH

AF:

0.00536

GnomAD3 exomes

AF:

0.00172

AC:

273

AN:

158465

Hom.:

AF XY:

0.00211

AC XY:

120

AN XY:

56915

show subpopulations

Gnomad AFR exome

AF:

0.000281

Gnomad AMR exome

AF:

0.000977

Gnomad ASJ exome

AF:

0.00573

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00371

Gnomad FIN exome

AF:

0.000126

Gnomad NFE exome

AF:

0.00164

Gnomad OTH exome

AF:

0.00460

GnomAD4 exome

AF:

0.00194

AC:

860

AN:

442609

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

368

AN XY:

165151

show subpopulations

Gnomad4 AFR exome

AF:

0.000502

Gnomad4 AMR exome

AF:

0.000938

Gnomad4 ASJ exome

AF:

0.00619

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00401

Gnomad4 FIN exome

AF:

0.0000706

Gnomad4 NFE exome

AF:

0.00159

Gnomad4 OTH exome

AF:

0.00296

GnomAD4 genome

AF:

0.00119

AC:

133

AN:

112132

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

34320

show subpopulations

Gnomad4 AFR

AF:

0.0000970

Gnomad4 AMR

AF:

0.00254

Gnomad4 ASJ

AF:

0.00454

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00255

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00136

Gnomad4 OTH

AF:

0.00529

Alfa

AF:

0.00239

Hom.:

Bravo

AF:

0.00156

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

Sep 09, 2024

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

-0.85

CADD

Benign

0.28

DANN

Benign

0.64

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