rs369390009

Variant names:

• chrX-644919-A-AAG
• rs369390009
• NM_000451.4:c.*284_*285dupAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000451.4(SHOX):​c.*284_*285dupAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 432,518 control chromosomes in the GnomAD database, including 6,669 homozygotes. There are 36,827 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.16 (2073 hom., 11624 hem., cov: 29)
  • Exomes 𝑓: 0.18 (4596 hom. 25203 hem.)
• Consequence: SHOX NM_000451.4 3_prime_UTR
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.336

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHOX	NM_000451.4	c.*284_*285dupAG		3_prime_UTR_variant	Exon 5 of 5	ENST00000686671.1	NP_000442.1
SHOX	NM_006883.2	c.633+3833_633+3834dupAG		intron_variant	Intron 5 of 5		NP_006874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHOX	ENST00000686671.1	c.*284_*285dupAG		3_prime_UTR_variant	Exon 5 of 5		NM_000451.4	ENSP00000508521.1
SHOX	ENST00000381575.6	c.633+3833_633+3834dupAG		intron_variant	Intron 4 of 4	1		ENSP00000370987.1
SHOX	ENST00000381578.6	c.*284_*285dupAG		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000370990.1
SHOX	ENST00000334060.8	c.633+3833_633+3834dupAG		intron_variant	Intron 5 of 5	5		ENSP00000335505.3

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24110 AN: 151980 Hom.: 2072 Cov.: 29 AF XY: 0.156 AC XY: 11612 AN XY: 74222

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.0950

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.176 AC: 49285 AN: 280420 Hom.: 4596 Cov.: 3 AF XY: 0.176 AC XY: 25203 AN XY: 143316

Gnomad4 AFR exome AF: 0.0962

Gnomad4 AMR exome AF: 0.202

Gnomad4 ASJ exome AF: 0.262

Gnomad4 EAS exome AF: 0.0930

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.159 AC: 24115 AN: 152098 Hom.: 2073 Cov.: 29 AF XY: 0.156 AC XY: 11624 AN XY: 74350

Gnomad4 AFR AF: 0.0953

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.0950

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.183

Bravo AF: 0.167

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

SHOX-related short stature Uncertain:1

Mar 03, 2016

Human Genetics Disease in Children – Taif University, Taif University

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs369390009; hg19: chrX-605654;