Variant rs749355015 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_000451.4(SHOX):c.*41C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,396,558 control chromosomes in the GnomAD database, including 15 homozygotes. There are 1,019 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 0.0048 ( 7 hom., 371 hem., cov: 33)

Exomes 𝑓: 0.0011 ( 8 hom. 648 hem. )

Consequence

SHOX
NM_000451.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 0.329

Variant links:

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]

SHOX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00111 (1376/1244334) while in subpopulation AFR AF= 0.0181 (440/24284). AF 95% confidence interval is 0.0167. There are 8 homozygotes in gnomad4_exome. There are 648 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHOX	NM_000451.4 linkuse as main transcript	c.*41C>A		3_prime_UTR_variant	5/5	ENST00000686671.1	NP_000442.1
SHOX	NM_006883.2 linkuse as main transcript	c.633+3590C>A		intron_variant			NP_006874.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHOX	ENST00000686671.1 linkuse as main transcript	c.*41C>A	3_prime_UTR_variant	5/5		NM_000451.4	ENSP00000508521	P1	O15266-1
SHOX	ENST00000381575.6 linkuse as main transcript	c.633+3590C>A	intron_variant		1		ENSP00000370987		O15266-2
SHOX	ENST00000381578.6 linkuse as main transcript	c.*41C>A	3_prime_UTR_variant	6/6	5		ENSP00000370990	P1	O15266-1
SHOX	ENST00000334060.8 linkuse as main transcript	c.633+3590C>A	intron_variant		5		ENSP00000335505		O15266-2

Frequencies

GnomAD3 genomes

AF:

0.00477

AC:

725

AN:

152112

Hom.:

Cov.:

AF XY:

0.00494

AC XY:

367

AN XY:

74300

show subpopulations

Gnomad AFR

AF:

0.0146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00182

AC:

AN:

13208

Hom.:

AF XY:

0.00230

AC XY:

AN XY:

7394

show subpopulations

Gnomad AFR exome

AF:

0.0289

Gnomad AMR exome

AF:

0.00308

Gnomad ASJ exome

AF:

0.00372

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000657

Gnomad OTH exome

AF:

0.00195

GnomAD4 exome

AF:

0.00111

AC:

1376

AN:

1244334

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

648

AN XY:

607386

show subpopulations

Gnomad4 AFR exome

AF:

0.0181

Gnomad4 AMR exome

AF:

0.00263

Gnomad4 ASJ exome

AF:

0.000686

Gnomad4 EAS exome

AF:

0.0000352

Gnomad4 SAS exome

AF:

0.000279

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000719

Gnomad4 OTH exome

AF:

0.00251

GnomAD4 genome

AF:

0.00480

AC:

731

AN:

152224

Hom.:

Cov.:

AF XY:

0.00499

AC XY:

371

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0147

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.00284

Bravo

AF:

0.00553

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SHOX-related short stature

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Human Genetics Disease in Children – Taif University, Taif University

Mar 03, 2016

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.1

DANN

Benign

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over