chrX-624523-C-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_006883.2(SHOX):c.-512C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 152,102 control chromosomes in the GnomAD database, including 74 homozygotes. There are 2,048 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.029 ( 74 hom., 2045 hem., cov: 30)
Exomes 𝑓: 0.038 ( 0 hom. 3 hem. )
Consequence
SHOX
NM_006883.2 5_prime_UTR
NM_006883.2 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0200
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant X-624523-C-A is Benign according to our data. Variant chrX-624523-C-A is described in ClinVar as [Benign]. Clinvar id is 191362.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0288 (4383/152024) while in subpopulation AFR AF= 0.0413 (1711/41470). AF 95% confidence interval is 0.0396. There are 74 homozygotes in gnomad4. There are 2045 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 73 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHOX | NM_006883.2 | c.-512C>A | 5_prime_UTR_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHOX | ENST00000334060.8 | c.-512C>A | 5_prime_UTR_variant | 1/6 | 5 | ||||
SHOX | ENST00000381578.6 | c.-512C>A | 5_prime_UTR_variant | 1/6 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0289 AC: 4384AN: 151906Hom.: 73 Cov.: 30 AF XY: 0.0275 AC XY: 2041AN XY: 74170
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GnomAD4 exome AF: 0.0385 AC: 3AN: 78Hom.: 0 Cov.: 0 AF XY: 0.0536 AC XY: 3AN XY: 56
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GnomAD4 genome ? AF: 0.0288 AC: 4383AN: 152024Hom.: 74 Cov.: 30 AF XY: 0.0275 AC XY: 2045AN XY: 74298
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ClinVar
Significance: Benign
Submissions summary: Pathogenic:1Benign:4
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
SHOX-related short stature Pathogenic:1Benign:1
Benign, no assertion criteria provided | curation | Reproductive Health Research and Development, BGI Genomics | Jan 06, 2020 | NM_000451.3:c.-512C>A in SHOX gene has an allele frequency of 0.042 in African subpopulation in the gnomAD database, including 15 homozygous occurrences. Taken together, we interprete this variant as Benign/Likely benign variant. ACMG/AMP criteria applied: BS1, BS2. - |
Pathogenic, no assertion criteria provided | not provided | Genetics Research Lab, Taif University | - | - - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
SHOX-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 19, 2022 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Computational scores
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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