X-630879-G-C

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.-19G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000329 in 1,612,316 control chromosomes in the GnomAD database, including 8 homozygotes. There are 230 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (5 hom., 124 hem., cov: 33)
  • Exomes 𝑓: 0.00017 (3 hom. 106 hem.)
• Consequence: SHOX NM_000451.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.520

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=-0.86).
• BP6: Variant X-630879-G-C is Benign according to our data. Variant chrX-630879-G-C is described in ClinVar as [Benign]. Clinvar id is 448372.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-630879-G-C is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAd at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHOX	NM_000451.4	c.-19G>C		5_prime_UTR_variant	1/5	ENST00000686671.1
SHOX	NM_006883.2	c.-19G>C		5_prime_UTR_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHOX	ENST00000686671.1	c.-19G>C		5_prime_UTR_variant	1/5		NM_000451.4	P1
SHOX	ENST00000381575.6	c.-19G>C		5_prime_UTR_variant	1/5	1
SHOX	ENST00000334060.8	c.-19G>C		5_prime_UTR_variant	2/6	5
SHOX	ENST00000381578.6	c.-19G>C		5_prime_UTR_variant	2/6	5		P1

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 284 AN: 152146 Hom.: 5 Cov.: 33 AF XY: 0.00167 AC XY: 124 AN XY: 74328

Gnomad AFR AF: 0.00649

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000506 AC: 126 AN: 248958 Hom.: 1 AF XY: 0.000318 AC XY: 43 AN XY: 135288

Gnomad AFR exome AF: 0.00723

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000168 AC: 246 AN: 1460052 Hom.: 3 Cov.: 30 AF XY: 0.000146 AC XY: 106 AN XY: 726258

Gnomad4 AFR exome AF: 0.00634

Gnomad4 AMR exome AF: 0.000313

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.000265

GnomAD4 genome AF: 0.00187 AC: 284 AN: 152264 Hom.: 5 Cov.: 33 AF XY: 0.00167 AC XY: 124 AN XY: 74456

Gnomad4 AFR AF: 0.00647

Gnomad4 AMR AF: 0.000784

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000946

Bravo AF: 0.00212

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Oct 28, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	7.2
Dann	Benign	0.39

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: rs201157428; hg19: chrX-591614;