Variant X-73823462-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000429829.6(XIST):n.16439C>T 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 0.0126 in 514,253 control chromosomes in the GnomAD database, including 317 homozygotes. There are 1,674 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 0.039 ( 239 hom., 1080 hem., cov: 22)

Exomes 𝑓: 0.0055 ( 78 hom. 594 hem. )

Consequence

XIST
ENST00000429829.6 non_coding_transcript_exon

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.321

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=-0.96).

BP6

Variant X-73823462-G-A is Benign according to our data. Variant chrX-73823462-G-A is described in ClinVar as [Benign]. Clinvar id is 3041924.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 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.16469C>T		non_coding_transcript_exon_variant	6/6
TSIX	NR_003255.2 linkuse as main transcript	n.31258G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL
XIST	ENST00000429829.6 linkuse as main transcript	n.16439C>T	non_coding_transcript_exon_variant	6/6	1
TSIX	ENST00000604411.1 linkuse as main transcript	n.31258G>A	non_coding_transcript_exon_variant	1/1	6
XIST	ENST00000648970.1 linkuse as main transcript	n.6403C>T	non_coding_transcript_exon_variant	7/7

Frequencies

GnomAD3 genomes

AF:

0.0386

AC:

4267

AN:

110511

Hom.:

239

Cov.:

AF XY:

0.0329

AC XY:

1077

AN XY:

32723

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000384

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00426

Gnomad NFE

AF:

0.000359

Gnomad OTH

AF:

0.0324

GnomAD3 exomes

AF:

0.00895

AC:

875

AN:

97779

Hom.:

AF XY:

0.00647

AC XY:

229

AN XY:

35415

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.00762

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000212

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000348

Gnomad OTH exome

AF:

0.00521

GnomAD4 exome

AF:

0.00554

AC:

2235

AN:

403699

Hom.:

Cov.:

AF XY:

0.00397

AC XY:

594

AN XY:

149471

show subpopulations

Gnomad4 AFR exome

AF:

0.131

Gnomad4 AMR exome

AF:

0.00836

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000236

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000247

Gnomad4 OTH exome

AF:

0.0119

GnomAD4 genome

AF:

0.0386

AC:

4268

AN:

110554

Hom.:

239

Cov.:

AF XY:

0.0330

AC XY:

1080

AN XY:

32776

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.0138

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000385

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000359

Gnomad4 OTH

AF:

0.0320

Alfa

AF:

0.0206

Hom.:

100

Bravo

AF:

0.0453

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

Feb 24, 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

-0.96

CADD

Benign

2.4

DANN

Benign

0.35

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