ENST00000429829.6:n.10104T>C

Variant names:

• chrX-73842620-A-G
• rs112769630
• ENST00000429829.7:n.10095T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000429829.7(XIST):​n.10095T>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 ENST00000429829.7 non_coding_transcript_exon
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.221
• Publications: 1 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 -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIST	NR_001564.3	MANE Select	n.10095T>C		non_coding_transcript_exon	Exon 1 of 6
	XIST	NR_190997.1		n.10095T>C		non_coding_transcript_exon	Exon 1 of 8
	XIST	NR_190999.1		n.10095T>C		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIST	ENST00000429829.7	TSL:1 MANE Select	n.10095T>C		non_coding_transcript_exon	Exon 1 of 6
	XIST	ENST00000648607.1		n.1589T>C		non_coding_transcript_exon	Exon 1 of 6
	XIST	ENST00000648991.1		n.1464T>C		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 4887 AN: 111455 Hom.: 267 Cov.: 22

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

GnomAD2 exomes AF: 0.0140 AC: 2333 AN: 166922 AF XY: 0.0115

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 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

African (AFR) AF: 0.152 AC: 2132 AN: 13981

American (AMR) AF: 0.0109 AC: 375 AN: 34345

Ashkenazi Jewish (ASJ) AF: 0.00831 AC: 128 AN: 15403

East Asian (EAS) AF: 0.00 AC: 0 AN: 27170

South Asian (SAS) AF: 0.00647 AC: 272 AN: 42070

European-Finnish (FIN) AF: 0.000808 AC: 23 AN: 28467

Middle Eastern (MID) AF: 0.00924 AC: 28 AN: 3030

European-Non Finnish (NFE) AF: 0.00150 AC: 385 AN: 255865

Other (OTH) AF: 0.0145 AC: 360 AN: 24823

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

African (AFR) AF: 0.147 AC: 4511 AN: 30583

American (AMR) AF: 0.0196 AC: 205 AN: 10453

Ashkenazi Jewish (ASJ) AF: 0.00868 AC: 23 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3550

South Asian (SAS) AF: 0.00837 AC: 22 AN: 2629

European-Finnish (FIN) AF: 0.000661 AC: 4 AN: 6054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00122 AC: 65 AN: 53162

Other (OTH) AF: 0.0361 AC: 55 AN: 1525

Alfa AF: 0.0173 Hom.: 172

Bravo AF: 0.0509

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	XIST-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.12
DANN	Benign	0.61
PhyloP100		-0.22

Splicing

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

Other links and lift over

dbSNP: rs112769630; hg19: chrX-73062455;