chrX-73842999-G-C

Variant names:

• chrX-73842999-G-C
• rs145132185
• ENST00000429829.7:n.9716C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000429829.7(XIST):​n.9716C>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 0.00000225 in 445,321 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: not found (cov: 22)
  • Exomes 𝑓: 0.0000022 (0 hom. 0 hem.)
• Consequence: XIST ENST00000429829.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.9716C>G		non_coding_transcript_exon	Exon 1 of 6
	XIST	NR_190997.1		n.9716C>G		non_coding_transcript_exon	Exon 1 of 8
	XIST	NR_190999.1		n.9716C>G		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.9716C>G		non_coding_transcript_exon	Exon 1 of 6
	XIST	ENST00000648607.1		n.1210C>G		non_coding_transcript_exon	Exon 1 of 6
	XIST	ENST00000648991.1		n.1085C>G		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000225 AC: 1 AN: 445321 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 167419

African (AFR) AF: 0.00 AC: 0 AN: 13985

American (AMR) AF: 0.00 AC: 0 AN: 34365

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15408

East Asian (EAS) AF: 0.00 AC: 0 AN: 27179

South Asian (SAS) AF: 0.00 AC: 0 AN: 42130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28467

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3028

European-Non Finnish (NFE) AF: 0.00000391 AC: 1 AN: 255934

Other (OTH) AF: 0.00 AC: 0 AN: 24825

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.22
PhyloP100		-0.0080
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

Splicing

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

Other links and lift over

dbSNP: rs145132185; hg19: chrX-73062834;