ENST00000381578:c.-507G>C

Variant names:

• chrX-624528-G-C
• rs111549748
• ENST00000381578:c.-507G>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000381578(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 ENST00000381578 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 B:5
• 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]

ACMG classification

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
SHOX	NM_006883.2	c.-507G>C		5_prime_UTR_variant	Exon 1 of 6		NP_006874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHOX	ENST00000381578	c.-507G>C		5_prime_UTR_variant	Exon 1 of 6	5		ENSP00000370990.1
SHOX	ENST00000334060	c.-507G>C		5_prime_UTR_variant	Exon 1 of 6	5		ENSP00000335505.3

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42360 AN: 151736 Hom.: 6111 Cov.: 30 AF XY: 0.278 AC XY: 20615 AN XY: 74072

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.283 AC: 17 AN: 60 Hom.: 2 Cov.: 0 AF XY: 0.262 AC XY: 11 AN XY: 42

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.279 AC: 42375 AN: 151854 Hom.: 6115 Cov.: 30 AF XY: 0.278 AC XY: 20636 AN XY: 74200

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.291

Bravo AF: 0.275

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

SHOX-related short stature Pathogenic:1 Benign:1

Jan 06, 2020

Reproductive Health Research and Development, BGI Genomics

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: curation

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. -

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Genetics Research Lab, Taif University

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: not provided

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not specified Benign:2

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Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Leri-Weill dyschondrosteosis Benign:1

Dec 18, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Connective tissue disorder Benign:1

Apr 15, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
DANN	Benign	0.54

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: rs111549748; hg19: chrX-585263;