Variant X-630879-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.520

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:

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ACMG classification

Classification made for transcript

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 GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHOX	NM_000451.4 linkuse as main transcript	c.-19G>C		5_prime_UTR_variant	1/5	ENST00000686671.1	NP_000442.1	O15266-1A0A024R385
SHOX	NM_006883.2 linkuse as main transcript	c.-19G>C		5_prime_UTR_variant	2/6		NP_006874.1	O15266-2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SHOX	ENST00000686671 linkuse as main transcript	c.-19G>C	5_prime_UTR_variant	1/5		NM_000451.4	ENSP00000508521.1	O15266-1
SHOX	ENST00000381575 linkuse as main transcript	c.-19G>C	5_prime_UTR_variant	1/5	1		ENSP00000370987.1	O15266-2
SHOX	ENST00000381578 linkuse as main transcript	c.-19G>C	5_prime_UTR_variant	2/6	5		ENSP00000370990.1	O15266-1
SHOX	ENST00000334060 linkuse as main transcript	c.-19G>C	5_prime_UTR_variant	2/6	5		ENSP00000335505.3	O15266-2

Frequencies

GnomAD3 genomes

AF:

0.00187

AC:

284

AN:

152146

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

124

AN XY:

74328

show subpopulations

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.:

AF XY:

0.000318

AC XY:

AN XY:

135288

show subpopulations

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.:

Cov.:

AF XY:

0.000146

AC XY:

106

AN XY:

726258

show subpopulations

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.:

Cov.:

AF XY:

0.00167

AC XY:

124

AN XY:

74456

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Oct 28, 2016

- -

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

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