X-630442-TTGTCTCTC-T

Position:

• chrX-630442-TTGTCTCTC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_006883.2(SHOX):​c.-432-14_-432-7del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0055 in 200,936 control chromosomes in the GnomAD database, including 20 homozygotes. There are 529 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (20 hom., 504 hem., cov: 33)
  • Exomes 𝑓: 0.0010 (0 hom. 25 hem.)
• Consequence: SHOX NM_006883.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.15

Genes affected

SHOX (HGNC:10853): (SHOX homeobox) This gene belongs to the paired homeobox family and is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes. Defects in this gene are associated with idiopathic growth retardation and in the short stature phenotype of Turner syndrome patients. This gene is highly conserved across species from mammals to fish to flies. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-630442-TTGTCTCTC-T is Benign according to our data. Variant chrX-630442-TTGTCTCTC-T is described in ClinVar as [Likely_benign]. Clinvar id is 1702479.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00694 (1056/152224) while in subpopulation AFR AF= 0.0243 (1009/41562). AF 95% confidence interval is 0.023. There are 20 homozygotes in gnomad4. There are 504 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHOX	NM_006883.2	c.-432-14_-432-7del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHOX	ENST00000334060.8	c.-432-14_-432-7del		splice_polypyrimidine_tract_variant, intron_variant		5
SHOX	ENST00000381578.6	c.-432-14_-432-7del		splice_polypyrimidine_tract_variant, intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.00693 AC: 1054 AN: 152106 Hom.: 20 Cov.: 33 AF XY: 0.00677 AC XY: 503 AN XY: 74310

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00526

GnomAD4 exome AF: 0.00101 AC: 49 AN: 48712 Hom.: 0 AF XY: 0.00100 AC XY: 25 AN XY: 24916

Gnomad4 AFR exome AF: 0.0304

Gnomad4 AMR exome AF: 0.00168

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000329

Gnomad4 OTH exome AF: 0.000810

GnomAD4 genome AF: 0.00694 AC: 1056 AN: 152224 Hom.: 20 Cov.: 33 AF XY: 0.00677 AC XY: 504 AN XY: 74438

Gnomad4 AFR AF: 0.0243

Gnomad4 AMR AF: 0.00189

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00521

Bravo AF: 0.00768

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Connective tissue disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

May 01, 2020

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs767085863; hg19: chrX-591177;