rs193072890
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM1BP4_StrongBP6BS1BS2
The ENST00000381575.6(SHOX):c.653G>A(p.Arg218His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00495 in 375,812 control chromosomes in the GnomAD database, including 27 homozygotes. There are 927 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R218C) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000381575.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHOX | NM_006883.2 | c.653G>A | p.Arg218His | missense_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHOX | ENST00000381575.6 | c.653G>A | p.Arg218His | missense_variant | 5/5 | 1 | |||
SHOX | ENST00000334060.8 | c.653G>A | p.Arg218His | missense_variant | 6/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0120 AC: 1607AN: 134240Hom.: 22 Cov.: 28 AF XY: 0.0125 AC XY: 804AN XY: 64396
GnomAD3 exomes AF: 0.00129 AC: 125AN: 97022Hom.: 2 AF XY: 0.00107 AC XY: 57AN XY: 53472
GnomAD4 exome AF: 0.00104 AC: 252AN: 241466Hom.: 6 Cov.: 0 AF XY: 0.000856 AC XY: 120AN XY: 140114
GnomAD4 genome ? AF: 0.0120 AC: 1608AN: 134346Hom.: 21 Cov.: 28 AF XY: 0.0125 AC XY: 807AN XY: 64514
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 09, 2017 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 17, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | SHOX: BS1, BS2 - |
SHOX-related condition Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 20, 2019 | 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at