X-73846604-T-C

Variant names:

• chrX-73846604-T-C
• rs1894271
• ENST00000429829.7:n.6111A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000429829.7(XIST):​n.6111A>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 ENST00000429829.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640
• Publications: 9 publications found

Genes affected

XIST (HGNC:12810): (X inactive specific transcript) X inactivation is an early developmental process in mammalian females that transcriptionally silences one of the pair of X chromosomes, thus providing dosage equivalence between males and females. The process is regulated by several factors, including a region of chromosome X called the X inactivation center (XIC). The XIC comprises several non-coding and protein-coding genes, and this gene was the first non-coding gene identified within the XIC. This gene is expressed exclusively from the XIC of the inactive X chromosome, and is essential for the initiation and spread of X-inactivation. The transcript is a spliced RNA. Alternatively spliced transcript variants have been identified, but their full length sequences have not been determined. Mutations in the XIST promoter cause familial skewed X inactivation. [provided by RefSeq, Apr 2012]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000429829.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIST	NR_001564.3	MANE Select	n.6111A>G		non_coding_transcript_exon	Exon 1 of 6
	XIST	NR_190997.1		n.6111A>G		non_coding_transcript_exon	Exon 1 of 8
	XIST	NR_190999.1		n.6111A>G		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIST	ENST00000429829.7	TSL:1 MANE Select	n.6111A>G		non_coding_transcript_exon	Exon 1 of 6
	XIST	ENST00000650186.1		n.397A>G		non_coding_transcript_exon	Exon 1 of 7
	XIST	ENST00000650627.1		n.4989A>G		non_coding_transcript_exon	Exon 1 of 8

Frequencies

GnomAD3 genomes AF: 0.192 AC: 21270 AN: 110879 Hom.: 2210 Cov.: 23

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

GnomAD2 exomes AF: 0.269 AC: 45038 AN: 167372 AF XY: 0.277

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 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

African (AFR) AF: 0.119 AC: 1666 AN: 13987

American (AMR) AF: 0.212 AC: 7284 AN: 34378

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 2309 AN: 15411

East Asian (EAS) AF: 0.949 AC: 25791 AN: 27178

South Asian (SAS) AF: 0.422 AC: 17797 AN: 42141

European-Finnish (FIN) AF: 0.218 AC: 6201 AN: 28484

Middle Eastern (MID) AF: 0.109 AC: 330 AN: 3029

European-Non Finnish (NFE) AF: 0.177 AC: 45335 AN: 255910

Other (OTH) AF: 0.213 AC: 5298 AN: 24826

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

African (AFR) AF: 0.121 AC: 3706 AN: 30544

American (AMR) AF: 0.194 AC: 2037 AN: 10517

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 400 AN: 2635

East Asian (EAS) AF: 0.934 AC: 3217 AN: 3443

South Asian (SAS) AF: 0.428 AC: 1111 AN: 2596

European-Finnish (FIN) AF: 0.205 AC: 1218 AN: 5934

Middle Eastern (MID) AF: 0.146 AC: 31 AN: 213

European-Non Finnish (NFE) AF: 0.174 AC: 9217 AN: 52861

Other (OTH) AF: 0.175 AC: 264 AN: 1509

Alfa AF: 0.176 Hom.: 2160

Bravo AF: 0.191

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.77
DANN	Benign	0.81
PhyloP100		-0.64

Splicing

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

Other links and lift over

dbSNP: rs1894271; hg19: chrX-73066439;