X-73846604-T-C

Position:

• chrX-73846604-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000429829.6(XIST):​n.6120A>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 0.24 in 556,275 control chromosomes in the GnomAD database, including 16,192 homozygotes. There are 50,649 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (2207 hom., 6636 hem., cov: 23)
  • Exomes 𝑓: 0.25 (13985 hom. 44013 hem.)
• Consequence: XIST ENST00000429829.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640

Genes affected

XIST (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIST	NR_001564.2	n.6150A>G		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XIST	ENST00000429829.6	n.6120A>G		non_coding_transcript_exon_variant	1/6	1
XIST	ENST00000650186.1	n.397A>G		non_coding_transcript_exon_variant	1/7
XIST	ENST00000650627.1	n.4989A>G		non_coding_transcript_exon_variant	1/8

Frequencies

GnomAD3 genomes AF: 0.192 AC: 21270 AN: 110879 Hom.: 2210 Cov.: 23 AF XY: 0.200 AC XY: 6631 AN XY: 33155

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.170

GnomAD3 exomes AF: 0.269 AC: 45038 AN: 167372 Hom.: 6220 AF XY: 0.277 AC XY: 17582 AN XY: 63496

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.149

Gnomad EAS exome AF: 0.942

Gnomad SAS exome AF: 0.430

Gnomad FIN exome AF: 0.214

Gnomad NFE exome AF: 0.175

Gnomad OTH exome AF: 0.220

GnomAD4 exome AF: 0.252 AC: 112011 AN: 445344 Hom.: 13985 Cov.: 0 AF XY: 0.263 AC XY: 44013 AN XY: 167392

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.949

Gnomad4 SAS exome AF: 0.422

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.192 AC: 21276 AN: 110931 Hom.: 2207 Cov.: 23 AF XY: 0.200 AC XY: 6636 AN XY: 33217

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.934

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.175

Alfa AF: 0.176 Hom.: 2160

Bravo AF: 0.191

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.77
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1894271; hg19: chrX-73066439;