X-624386-C-CTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006883.2(SHOX):c.-637_-636dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (5071 hom., 18302 hem., cov: 0)
  • Exomes 𝑓: 0.045 (0 hom. 1 hem.)
• Consequence: SHOX NM_006883.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.14

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 -10 ACMG points.

• BP6: Variant X-624386-C-CTT is Benign according to our data. Variant chrX-624386-C-CTT is described in ClinVar as [Likely_benign]. Clinvar id is 3036935.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHOX	NM_006883.2	c.-637_-636dup		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHOX	ENST00000334060.8	c.-637_-636dup		5_prime_UTR_variant	1/6	5
SHOX	ENST00000381578.6	c.-637_-636dup		5_prime_UTR_variant	1/6	5		P1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 37782 AN: 130528 Hom.: 5067 Cov.: 0 AF XY: 0.290 AC XY: 18292 AN XY: 63022

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.0455 AC: 1 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 1 AN XY: 12

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.289 AC: 37793 AN: 130564 Hom.: 5071 Cov.: 0 AF XY: 0.290 AC XY: 18302 AN XY: 63068

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.298

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SHOX-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 16, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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: rs55872554; hg19: chrX-585121;