Variant ENST00000381575.6:c.653G>T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate

The ENST00000381575.6(SHOX):c.653G>T(p.Arg218Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R218H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 28)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

SHOX
ENST00000381575.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.627

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 Uncertain_significance. Variant got 0 ACMG points.

PM1

In a chain Short stature homeobox protein (size 291) in uniprot entity SHOX_HUMAN there are 94 pathogenic changes around while only 7 benign (93%) in ENST00000381575.6

BP4

Computational evidence support a benign effect (MetaRNN=0.0807493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHOX	NM_006883.2 link	c.653G>T	p.Arg218Leu	missense_variant	Exon 6 of 6		NP_006874.1	O15266-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHOX	ENST00000381575.6 link	c.653G>T	p.Arg218Leu	missense_variant	Exon 5 of 5	1		ENSP00000370987.1		O15266-2
SHOX	ENST00000334060.8 link	c.653G>T	p.Arg218Leu	missense_variant	Exon 6 of 6	5		ENSP00000335505.3		O15266-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

134260

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

64406

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

241518

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

140138

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

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

AF:

0.00

AC:

AN:

134260

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

64406

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

0.36

DANN

Benign

0.71

FATHMM_MKL

Benign

0.00093

LIST_S2

Benign

0.26

T;.

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.081

T;T

MetaSVM

Benign

-0.45

PROVEAN

Benign

2.0

N;N

REVEL

Benign

0.16

Sift

Benign

0.15

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.0020

B;B

Vest4

0.24

MutPred

0.49

Loss of MoRF binding (P = 0.0537);Loss of MoRF binding (P = 0.0537);

MVP

0.41

ClinPred

0.089

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over