Genetic Variant ENST00000429829.6:n.9094_9095delTG (chrX-73843628-GCA-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The ENST00000429829.7(XIST):n.9085_9086delTG 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 0.000339 in 556,992 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 64 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., 39 hem., cov: 22)

Exomes 𝑓: 0.00015 ( 0 hom. 25 hem. )

Consequence

XIST
ENST00000429829.7 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.176

Publications

0 publications found

Variant links:

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]

XIST links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP6

Variant X-73843628-GCA-G is Benign according to our data. Variant chrX-73843628-GCA-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3034421.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 39 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
XIST	NR_001564.3	MANE Select	n.9085_9086delTG	non_coding_transcript_exon	Exon 1 of 6
XIST	NR_190997.1		n.9085_9086delTG	non_coding_transcript_exon	Exon 1 of 8
XIST	NR_190999.1		n.9085_9086delTG	non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
XIST	ENST00000429829.7	TSL:1 MANE Select	n.9085_9086delTG	non_coding_transcript_exon	Exon 1 of 6
XIST	ENST00000648607.1		n.579_580delTG	non_coding_transcript_exon	Exon 1 of 6
XIST	ENST00000648991.1		n.454_455delTG	non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

122

AN:

112167

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00372

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000567

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000656

GnomAD2 exomes

AF:

0.000278

AC:

AN:

165399

AF XY:

0.000227

show subpopulations

Gnomad AFR exome

AF:

0.00354

Gnomad AMR exome

AF:

0.000222

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000235

GnomAD4 exome

AF:

0.000151

AC:

AN:

444777

Hom.:

AF XY:

0.000150

AC XY:

AN XY:

166923

show subpopulations

African (AFR)

AF:

0.00379

AC:

AN:

13981

American (AMR)

AF:

0.000291

AC:

AN:

34308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15391

East Asian (EAS)

AF:

0.00

AC:

AN:

27153

South Asian (SAS)

AF:

0.00

AC:

AN:

41954

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28432

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3029

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

255720

Other (OTH)

AF:

0.000161

AC:

AN:

24809

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00109

AC:

122

AN:

112215

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

34393

show subpopulations

African (AFR)

AF:

0.00372

AC:

115

AN:

30939

American (AMR)

AF:

0.000567

AC:

AN:

10590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3565

South Asian (SAS)

AF:

0.00

AC:

AN:

2669

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6093

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53266

Other (OTH)

AF:

0.000648

AC:

AN:

1543

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000996

Hom.:

Bravo

AF:

0.00120

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

XIST-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.18

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over