X-73842620-A-G

Position:

• chrX-73842620-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000429829.6(XIST):​n.10104T>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 556,661 control chromosomes in the GnomAD database, including 390 homozygotes. There are 2,565 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 (267 hom., 1353 hem., cov: 22)
  • Exomes 𝑓: 0.0083 (123 hom. 1212 hem.)
• Consequence: XIST ENST00000429829.6 non_coding_transcript_exon
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.221

Genes affected

XIST (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-73842620-A-G is Benign according to our data. Variant chrX-73842620-A-G is described in ClinVar as [Benign]. Clinvar id is 3039016.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	n.10134T>C		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XIST	ENST00000429829.6	n.10104T>C		non_coding_transcript_exon_variant	1/6	1
XIST	ENST00000648607.1	n.1589T>C		non_coding_transcript_exon_variant	1/6
XIST	ENST00000648991.1	n.1464T>C		non_coding_transcript_exon_variant	1/5

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 4887 AN: 111455 Hom.: 267 Cov.: 22 AF XY: 0.0403 AC XY: 1355 AN XY: 33625

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.00868

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00835

Gnomad FIN AF: 0.000661

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00122

Gnomad OTH AF: 0.0365

GnomAD3 exomes AF: 0.0140 AC: 2333 AN: 166922 Hom.: 112 AF XY: 0.0115 AC XY: 726 AN XY: 63092

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.0102

Gnomad ASJ exome AF: 0.00932

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00611

Gnomad FIN exome AF: 0.00120

Gnomad NFE exome AF: 0.00155

Gnomad OTH exome AF: 0.00839

GnomAD4 exome AF: 0.00832 AC: 3703 AN: 445154 Hom.: 123 Cov.: 0 AF XY: 0.00725 AC XY: 1212 AN XY: 167262

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.0109

Gnomad4 ASJ exome AF: 0.00831

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00647

Gnomad4 FIN exome AF: 0.000808

Gnomad4 NFE exome AF: 0.00150

Gnomad4 OTH exome AF: 0.0145

GnomAD4 genome AF: 0.0438 AC: 4885 AN: 111507 Hom.: 267 Cov.: 22 AF XY: 0.0402 AC XY: 1353 AN XY: 33687

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.0196

Gnomad4 ASJ AF: 0.00868

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00837

Gnomad4 FIN AF: 0.000661

Gnomad4 NFE AF: 0.00122

Gnomad4 OTH AF: 0.0361

Alfa AF: 0.0173 Hom.: 172

Bravo AF: 0.0509

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

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	-0.85
CADD	Benign	0.12
DANN	Benign	0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs112769630; hg19: chrX-73062455;