Variant X-73823963-T-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.15968A>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 0.00286 in 551,269 control chromosomes in the GnomAD database, including 20 homozygotes. There are 425 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 0.0086 ( 16 hom., 255 hem., cov: 22)

Exomes 𝑓: 0.0014 ( 4 hom. 170 hem. )

Consequence

XIST
NR_001564.2 non_coding_transcript_exon

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.856

Variant links:

Genes affected

XIST (HGNC:):

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=-0.8).

BP6

Variant X-73823963-T-C is Benign according to our data. Variant chrX-73823963-T-C is described in ClinVar as [Benign]. Clinvar id is 3049478.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00861 (959/111354) while in subpopulation AFR AF= 0.0296 (908/30670). AF 95% confidence interval is 0.028. There are 16 homozygotes in gnomad4. There are 255 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIST	NR_001564.2 linkuse as main transcript	n.15968A>G		non_coding_transcript_exon_variant	6/6
TSIX	NR_003255.2 linkuse as main transcript	n.31759T>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL
XIST	ENST00000429829.6 linkuse as main transcript	n.15938A>G	non_coding_transcript_exon_variant	6/6	1
TSIX	ENST00000604411.1 linkuse as main transcript	n.31759T>C	non_coding_transcript_exon_variant	1/1	6
XIST	ENST00000648970.1 linkuse as main transcript	n.5902A>G	non_coding_transcript_exon_variant	7/7

Frequencies

GnomAD3 genomes

AF:

0.00861

AC:

958

AN:

111305

Hom.:

Cov.:

AF XY:

0.00761

AC XY:

255

AN XY:

33489

show subpopulations

Gnomad AFR

AF:

0.0296

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00372

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000378

Gnomad OTH

AF:

0.00664

GnomAD3 exomes

AF:

0.00256

AC:

392

AN:

153006

Hom.:

AF XY:

0.00203

AC XY:

107

AN XY:

52694

show subpopulations

Gnomad AFR exome

AF:

0.0292

Gnomad AMR exome

AF:

0.00273

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000170

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000118

Gnomad OTH exome

AF:

0.000988

GnomAD4 exome

AF:

0.00141

AC:

620

AN:

439915

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

170

AN XY:

162777

show subpopulations

Gnomad4 AFR exome

AF:

0.0305

Gnomad4 AMR exome

AF:

0.00273

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000242

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000115

Gnomad4 OTH exome

AF:

0.00252

GnomAD4 genome

AF:

0.00861

AC:

959

AN:

111354

Hom.:

Cov.:

AF XY:

0.00760

AC XY:

255

AN XY:

33548

show subpopulations

Gnomad4 AFR

AF:

0.0296

Gnomad4 AMR

AF:

0.00372

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000378

Gnomad4 OTH

AF:

0.00655

Alfa

AF:

0.00386

Hom.:

Bravo

AF:

0.00934

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TSIX-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 09, 2019

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

-0.80

CADD

Benign

7.5

DANN

Benign

0.68

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