chrX-630442-TTGTCTCTC-T
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
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
NM_006883.2 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
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]
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ACMG classification
Classification made for transcript
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: 1054AN: 152106Hom.: 20 Cov.: 33 AF XY: 0.00677 AC XY: 503AN XY: 74310
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GnomAD4 exome AF: 0.00101 AC: 49AN: 48712Hom.: 0 AF XY: 0.00100 AC XY: 25AN XY: 24916
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GnomAD4 genome AF: 0.00694 AC: 1056AN: 152224Hom.: 20 Cov.: 33 AF XY: 0.00677 AC XY: 504AN XY: 74438
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
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 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at