chrX-624528-G-C
Position:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_006883.2(SHOX):c.-507G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,914 control chromosomes in the GnomAD database, including 6,117 homozygotes. There are 20,647 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.28 ( 6115 hom., 20636 hem., cov: 30)
Exomes 𝑓: 0.28 ( 2 hom. 11 hem. )
Consequence
SHOX
NM_006883.2 5_prime_UTR
NM_006883.2 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.581
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant X-624528-G-C is Benign according to our data. Variant chrX-624528-G-C is described in ClinVar as [Benign]. Clinvar id is 191361.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHOX | NM_006883.2 | c.-507G>C | 5_prime_UTR_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHOX | ENST00000334060.8 | c.-507G>C | 5_prime_UTR_variant | 1/6 | 5 | ||||
SHOX | ENST00000381578.6 | c.-507G>C | 5_prime_UTR_variant | 1/6 | 5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.279 AC: 42360AN: 151736Hom.: 6111 Cov.: 30 AF XY: 0.278 AC XY: 20615AN XY: 74072
GnomAD3 genomes
AF:
AC:
42360
AN:
151736
Hom.:
Cov.:
30
AF XY:
AC XY:
20615
AN XY:
74072
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.283 AC: 17AN: 60Hom.: 2 Cov.: 0 AF XY: 0.262 AC XY: 11AN XY: 42
GnomAD4 exome
AF:
AC:
17
AN:
60
Hom.:
Cov.:
0
AF XY:
AC XY:
11
AN XY:
42
Gnomad4 AFR exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.279 AC: 42375AN: 151854Hom.: 6115 Cov.: 30 AF XY: 0.278 AC XY: 20636AN XY: 74200
GnomAD4 genome
AF:
AC:
42375
AN:
151854
Hom.:
Cov.:
30
AF XY:
AC XY:
20636
AN XY:
74200
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
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.-507G>C in the gene SHOX has an allele frequency of 0.327 in East Asian subpopulation in the gnomAD database, including 1343 homozygous occurrences. This evidence suggests the variant to be classified as benign. ACMG/AMP criteria applied: BA1. - |
Pathogenic, no assertion criteria provided | not provided | Genetics Research Lab, Taif University | - | - - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Connective tissue disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Apr 15, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at