X-624386-C-CT

Position:

• chrX-624386-C-CT

Variant summary

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

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

• Frequency:
  • Genomes: 𝑓 0.20 (4573 hom., 12183 hem., cov: 0)
  • Exomes 𝑓: 0.045 (0 hom. 1 hem.)
• Consequence: SHOX NM_006883.2 5_prime_UTR
• Clinical Significance: 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-CT is Benign according to our data. Variant chrX-624386-C-CT is described in ClinVar as [Benign]. Clinvar id is 3036689.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.195 AC: 25532 AN: 130778 Hom.: 4563 Cov.: 0 AF XY: 0.192 AC XY: 12152 AN XY: 63160

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.0511

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0961

Gnomad EAS AF: 0.0990

Gnomad SAS AF: 0.0392

Gnomad FIN AF: 0.0583

Gnomad MID AF: 0.235

Gnomad NFE AF: 0.0636

Gnomad OTH AF: 0.177

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: 0.195 AC: 25564 AN: 130816 Hom.: 4573 Cov.: 0 AF XY: 0.193 AC XY: 12183 AN XY: 63208

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.0961

Gnomad4 EAS AF: 0.0993

Gnomad4 SAS AF: 0.0382

Gnomad4 FIN AF: 0.0583

Gnomad4 NFE AF: 0.0635

Gnomad4 OTH AF: 0.175

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SHOX-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 16, 2021

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: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;