rs145132185

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-73842999-G-A
• chrX-73842999-G-C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The ENST00000429829.7(XIST):​n.9716C>T 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 0.00271 in 556,789 control chromosomes in the GnomAD database, including 3 homozygotes. There are 532 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., 72 hem., cov: 22)
  • Exomes 𝑓: 0.0028 (2 hom. 460 hem.)
• Consequence: XIST ENST00000429829.7 non_coding_transcript_exon
• Clinical Significance: Likely benign no assertion criteria provided B:1
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant X-73842999-G-A is Benign according to our data. Variant chrX-73842999-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3040456.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Hemizygotes in GnomAd4 at 72 XL gene

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

Frequencies

GnomAD3 genomes AF: 0.00222 AC: 247 AN: 111421 Hom.: 1 Cov.: 22

Gnomad AFR AF: 0.000359

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00872

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000828

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00390

Gnomad OTH AF: 0.000668

GnomAD2 exomes AF: 0.00263 AC: 441 AN: 167434 AF XY: 0.00261

Gnomad AFR exome AF: 0.000360

Gnomad AMR exome AF: 0.0000736

Gnomad ASJ exome AF: 0.00589

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00204

Gnomad NFE exome AF: 0.00473

Gnomad OTH exome AF: 0.00233

GnomAD4 exome AF: 0.00284 AC: 1264 AN: 445321 Hom.: 2 Cov.: 0 AF XY: 0.00275 AC XY: 460 AN XY: 167419

African (AFR) AF: 0.000501 AC: 7 AN: 13985

American (AMR) AF: 0.0000873 AC: 3 AN: 34365

Ashkenazi Jewish (ASJ) AF: 0.00558 AC: 86 AN: 15408

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

South Asian (SAS) AF: 0.0000237 AC: 1 AN: 42130

European-Finnish (FIN) AF: 0.00165 AC: 47 AN: 28467

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

European-Non Finnish (NFE) AF: 0.00419 AC: 1073 AN: 255934

Other (OTH) AF: 0.00189 AC: 47 AN: 24825

GnomAD4 genome AF: 0.00222 AC: 247 AN: 111468 Hom.: 1 Cov.: 22 AF XY: 0.00214 AC XY: 72 AN XY: 33668

African (AFR) AF: 0.000358 AC: 11 AN: 30737

American (AMR) AF: 0.00 AC: 0 AN: 10460

Ashkenazi Jewish (ASJ) AF: 0.00872 AC: 23 AN: 2637

East Asian (EAS) AF: 0.00 AC: 0 AN: 3526

South Asian (SAS) AF: 0.00 AC: 0 AN: 2625

European-Finnish (FIN) AF: 0.000828 AC: 5 AN: 6036

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

European-Non Finnish (NFE) AF: 0.00390 AC: 207 AN: 53031

Other (OTH) AF: 0.000660 AC: 1 AN: 1515

Alfa AF: 0.00338 Hom.: 25

Bravo AF: 0.00188

ClinVar

ClinVar submissions as Germline

Significance: Likely 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	-0.86
CADD	Benign	1.2
DANN	Benign	0.43
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;