X-630421-C-T

Variant summary

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

The NM_006883.2(SHOX):c.-432-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 160,122 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 185 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 0.0026 (0 hom., 172 hem., cov: 33)
  • Exomes 𝑓: 0.0035 (0 hom. 13 hem.)
• Consequence: SHOX NM_006883.2 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.396

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=-0.82).
• BS2: High Hemizygotes in GnomAd at 172 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHOX	NM_006883.2	c.-432-45C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHOX	ENST00000334060.8	c.-432-45C>T		intron_variant		5
SHOX	ENST00000381578.6	c.-432-45C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.00261 AC: 397 AN: 152112 Hom.: 0 Cov.: 33 AF XY: 0.00231 AC XY: 172 AN XY: 74316

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00499

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.00355 AC: 28 AN: 7892 Hom.: 0 Cov.: 0 AF XY: 0.00331 AC XY: 13 AN XY: 3928

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 NFE exome AF: 0.00541

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00261 AC: 397 AN: 152230 Hom.: 0 Cov.: 33 AF XY: 0.00231 AC XY: 172 AN XY: 74444

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.00499

Gnomad4 OTH AF: 0.00189

Bravo AF: 0.00266

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)

Dec 21, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.6
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs773802131; hg19: chrX-591156;