X-630382-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006883.2(SHOX):c.-432-84C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00506 in 160,950 control chromosomes in the GnomAD database, including 2 homozygotes. There are 399 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0052 (2 hom., 388 hem., cov: 33)
  • Exomes 𝑓: 0.0026 (0 hom. 11 hem.)
• Consequence: SHOX NM_006883.2 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.730

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High Homozygotes in GnomAd at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHOX	NM_006883.2	c.-432-84C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHOX	ENST00000334060.8	c.-432-84C>G		intron_variant		5
SHOX	ENST00000381578.6	c.-432-84C>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.00521 AC: 792 AN: 152104 Hom.: 2 Cov.: 33 AF XY: 0.00522 AC XY: 388 AN XY: 74296

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.0108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00825

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00264 AC: 23 AN: 8728 Hom.: 0 AF XY: 0.00252 AC XY: 11 AN XY: 4372

Gnomad4 AFR exome AF: 0.0104

Gnomad4 AMR exome AF: 0.00174

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00143

Gnomad4 FIN exome AF: 0.00769

Gnomad4 NFE exome AF: 0.00331

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00520 AC: 792 AN: 152222 Hom.: 2 Cov.: 33 AF XY: 0.00521 AC XY: 388 AN XY: 74424

Gnomad4 AFR AF: 0.00140

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00581

Gnomad4 FIN AF: 0.0108

Gnomad4 NFE AF: 0.00825

Gnomad4 OTH AF: 0.00142

Bravo AF: 0.00446

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Nov 16, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	8.3
Dann	Benign	0.24

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: rs768130629; hg19: chrX-591117;