dbSNP rs950355194: SHOX:c.-646T>G (chrX-624389-T-G) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The NM_006883.2(SHOX):c.-646T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000681 in 146,892 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000068 ( 0 hom., 5 hem., cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

SHOX
NM_006883.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.40

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant X-624389-T-G is Benign according to our data. Variant chrX-624389-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2659855.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHOX	NM_006883.2 link	c.-646T>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6		NP_006874.1	O15266-2
SHOX	NM_006883.2 link	c.-646T>G		5_prime_UTR_variant	Exon 1 of 6		NP_006874.1	O15266-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
SHOX	ENST00000381578 link	c.-646T>G	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	5	ENSP00000370990.1	O15266-1
SHOX	ENST00000334060 link	c.-646T>G	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	5	ENSP00000335505.3	O15266-2
SHOX	ENST00000381578 link	c.-646T>G	5_prime_UTR_variant	Exon 1 of 6	5	ENSP00000370990.1	O15266-1
SHOX	ENST00000334060 link	c.-646T>G	5_prime_UTR_variant	Exon 1 of 6	5	ENSP00000335505.3	O15266-2

Frequencies

GnomAD3 genomes

AF:

0.0000681

AC:

AN:

146892

Hom.:

Cov.:

AF XY:

0.0000698

AC XY:

AN XY:

71628

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000152

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 AFR exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000681

AC:

AN:

146892

Hom.:

Cov.:

AF XY:

0.0000698

AC XY:

AN XY:

71628

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000152

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000945

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SHOX: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.28

DANN

Benign

0.20

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