rs181143203
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_000451.4(SHOX):c.278-15C>A 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 0.000381 in 1,612,738 control chromosomes in the GnomAD database, including 9 homozygotes. There are 316 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00037 ( 0 hom., 34 hem., cov: 32)
Exomes 𝑓: 0.00038 ( 9 hom. 282 hem. )
Consequence
SHOX
NM_000451.4 splice_polypyrimidine_tract, intron
NM_000451.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.874
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 -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant X-634603-C-A is Benign according to our data. Variant chrX-634603-C-A is described in ClinVar as [Benign]. Clinvar id is 256194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-634603-C-A is described in Lovd as [Benign].
BS2
?
High Hemizygotes in GnomAd4 at 34 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHOX | NM_000451.4 | c.278-15C>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000686671.1 | |||
SHOX | NM_006883.2 | c.278-15C>A | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHOX | ENST00000686671.1 | c.278-15C>A | splice_polypyrimidine_tract_variant, intron_variant | NM_000451.4 | P1 | ||||
SHOX | ENST00000381575.6 | c.278-15C>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | |||||
SHOX | ENST00000334060.8 | c.278-15C>A | splice_polypyrimidine_tract_variant, intron_variant | 5 | |||||
SHOX | ENST00000381578.6 | c.278-15C>A | splice_polypyrimidine_tract_variant, intron_variant | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000368 AC: 56AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.000457 AC XY: 34AN XY: 74360
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GnomAD3 exomes AF: 0.00117 AC: 291AN: 248876Hom.: 3 AF XY: 0.00102 AC XY: 138AN XY: 134898
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GnomAD4 exome AF: 0.000382 AC: 558AN: 1460418Hom.: 9 Cov.: 33 AF XY: 0.000388 AC XY: 282AN XY: 726434
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GnomAD4 genome ? AF: 0.000368 AC: 56AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.000456 AC XY: 34AN XY: 74488
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 21, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
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