X-624387-T-TTTG

Variant summary

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

The NM_006883.2(SHOX):c.-646_-645insGTT 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 0.58 (6271 hom., 19293 hem., cov: 0)
  • Exomes 𝑓: 0.23 (0 hom. 2 hem.)
  • Failed GnomAD Quality Control
• Consequence: SHOX NM_006883.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.08

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-624387-T-TTTG is Benign according to our data. Variant chrX-624387-T-TTTG is described in ClinVar as [Likely_benign]. Clinvar id is 3036731.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHOX	NM_006883.2	c.-646_-645insGTT		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHOX	ENST00000334060.8	c.-646_-645insGTT		5_prime_UTR_variant	1/6	5
SHOX	ENST00000381578.6	c.-646_-645insGTT		5_prime_UTR_variant	1/6	5		P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 39849 AN: 68864 Hom.: 6276 Cov.: 0 AF XY: 0.579 AC XY: 19298 AN XY: 33322 FAILED QC

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.597

GnomAD4 exome AF: 0.227 AC: 5 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.143 AC XY: 2 AN XY: 14

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.222

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.579 AC: 39827 AN: 68830 Hom.: 6271 Cov.: 0 AF XY: 0.579 AC XY: 19293 AN XY: 33314

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.597

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

May 04, 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: rs200223988; hg19: chrX-585122;