chrX-630843-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_000451.4(SHOX):c.-55C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00391 in 1,607,792 control chromosomes in the GnomAD database, including 20 homozygotes. There are 3,012 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0030 ( 3 hom., 199 hem., cov: 33)
Exomes 𝑓: 0.0040 ( 17 hom. 2813 hem. )
Consequence
SHOX
NM_000451.4 5_prime_UTR
NM_000451.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.54
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 -8 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BS2
?
High Homozygotes in GnomAd at 3 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHOX | NM_000451.4 | c.-55C>T | 5_prime_UTR_variant | 1/5 | ENST00000686671.1 | ||
SHOX | NM_006883.2 | c.-55C>T | 5_prime_UTR_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHOX | ENST00000686671.1 | c.-55C>T | 5_prime_UTR_variant | 1/5 | NM_000451.4 | P1 | |||
SHOX | ENST00000381575.6 | c.-55C>T | 5_prime_UTR_variant | 1/5 | 1 | ||||
SHOX | ENST00000334060.8 | c.-55C>T | 5_prime_UTR_variant | 2/6 | 5 | ||||
SHOX | ENST00000381578.6 | c.-55C>T | 5_prime_UTR_variant | 2/6 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00298 AC: 454AN: 152166Hom.: 3 Cov.: 33 AF XY: 0.00268 AC XY: 199AN XY: 74332
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GnomAD4 exome AF: 0.00401 AC: 5840AN: 1455508Hom.: 17 Cov.: 29 AF XY: 0.00389 AC XY: 2813AN XY: 723758
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GnomAD4 genome ? AF: 0.00298 AC: 454AN: 152284Hom.: 3 Cov.: 33 AF XY: 0.00267 AC XY: 199AN XY: 74460
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Clinical Genetics and Genomics, Karolinska University Hospital | May 20, 2015 | - - |
Connective tissue disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Apr 21, 2020 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 17, 2018 | - - |
SHOX-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 15, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at