rs778186580

chrX-630887-CG-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_000451.4(SHOX):c.-9del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000624 in 1,612,664 control chromosomes in the GnomAD database, including 2 homozygotes. There are 517 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., 23 hem., cov: 33)
  • Exomes 𝑓: 0.00065 (2 hom. 494 hem.)
• Consequence: SHOX NM_000451.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.25

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant X-630887-CG-C is Benign according to our data. Variant chrX-630887-CG-C is described in ClinVar as [Likely_benign]. Clinvar id is 586583.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 23 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHOX	NM_000451.4	c.-9del		5_prime_UTR_variant	1/5	ENST00000686671.1
SHOX	NM_006883.2	c.-9del		5_prime_UTR_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHOX	ENST00000686671.1	c.-9del		5_prime_UTR_variant	1/5		NM_000451.4	P1
SHOX	ENST00000381575.6	c.-9del		5_prime_UTR_variant	1/5	1
SHOX	ENST00000334060.8	c.-9del		5_prime_UTR_variant	2/6	5
SHOX	ENST00000381578.6	c.-9del		5_prime_UTR_variant	2/6	5		P1

Frequencies

GnomAD3 genomes AF: 0.000394 AC: 60 AN: 152172 Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23 AN XY: 74326

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000437 AC: 109 AN: 249470 Hom.: 0 AF XY: 0.000443 AC XY: 60 AN XY: 135394

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000953

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000648 AC: 946 AN: 1460492 Hom.: 2 Cov.: 30 AF XY: 0.000680 AC XY: 494 AN XY: 726518

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000380

Gnomad4 NFE exome AF: 0.000828

Gnomad4 OTH exome AF: 0.000348

GnomAD4 genome AF: 0.000394 AC: 60 AN: 152172 Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23 AN XY: 74326

Gnomad4 AFR AF: 0.0000965

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000794

Gnomad4 OTH AF: 0.000478

Bravo AF: 0.000397

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Dec 01, 2020

- -

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: rs778186580; hg19: chrX-591622;