rs139059497

chrX-631017-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000451.4(SHOX):c.120G>A(p.Glu40=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000143 in 1,613,852 control chromosomes in the GnomAD database, including 1 homozygotes. There are 105 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. E40E) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., 42 hem., cov: 34)
  • Exomes 𝑓: 0.000090 (1 hom. 63 hem.)
• Consequence: SHOX NM_000451.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.84

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant X-631017-G-A is Benign according to our data. Variant chrX-631017-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 256192.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-631017-G-A is described in Lovd as [Benign].
• BS2: High Hemizygotes in GnomAd at 42 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHOX	NM_000451.4	c.120G>A	p.Glu40=	synonymous_variant	1/5	ENST00000686671.1
SHOX	NM_006883.2	c.120G>A	p.Glu40=	synonymous_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHOX	ENST00000686671.1	c.120G>A	p.Glu40=	synonymous_variant	1/5		NM_000451.4	P1
SHOX	ENST00000381575.6	c.120G>A	p.Glu40=	synonymous_variant	1/5	1
SHOX	ENST00000381578.6	c.120G>A	p.Glu40=	synonymous_variant	2/6	5		P1
SHOX	ENST00000334060.8	c.120G>A	p.Glu40=	synonymous_variant	2/6	5

Frequencies

GnomAD3 genomes AF: 0.000651 AC: 99 AN: 152164 Hom.: 0 Cov.: 34 AF XY: 0.000565 AC XY: 42 AN XY: 74338

Gnomad AFR AF: 0.00224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000227 AC: 57 AN: 250832 Hom.: 1 AF XY: 0.000236 AC XY: 32 AN XY: 135686

Gnomad AFR exome AF: 0.00246

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000903 AC: 132 AN: 1461570 Hom.: 1 Cov.: 30 AF XY: 0.0000866 AC XY: 63 AN XY: 727082

Gnomad4 AFR exome AF: 0.00227

Gnomad4 AMR exome AF: 0.000313

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: 0.0000225

Gnomad4 OTH exome AF: 0.000182

GnomAD4 genome AF: 0.000650 AC: 99 AN: 152282 Hom.: 0 Cov.: 34 AF XY: 0.000564 AC XY: 42 AN XY: 74466

Gnomad4 AFR AF: 0.00224

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000771

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

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	8.6
Dann	Uncertain	0.98

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: rs139059497; hg19: chrX-591752;