Variant 10-72007522-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate

The NM_004273.5(CHST3):c.491C>T(p.Pro164Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,451,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. P164P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

CHST3
NM_004273.5 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.84

Variant links:

Genes affected

CHST3 (HGNC:1971): (carbohydrate sulfotransferase 3) This gene encodes an enzyme which catalyzes the sulfation of chondroitin, a proteoglycan found in the extracellular matrix and most cells which is involved in cell migration and differentiation. Mutations in this gene are associated with spondylepiphyseal dysplasia and humerospinal dysostosis. [provided by RefSeq, Mar 2009]

CHST3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PM1

In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 4 uncertain in NM_004273.5

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.992

PP5

Variant 10-72007522-C-T is Pathogenic according to our data. Variant chr10-72007522-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 478823.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CHST3	NM_004273.5 linkuse as main transcript	c.491C>T	p.Pro164Leu	missense_variant	3/3	ENST00000373115.5
CHST3	XM_006718075.5 linkuse as main transcript	c.491C>T	p.Pro164Leu	missense_variant	3/3
CHST3	XM_011540369.3 linkuse as main transcript	c.491C>T	p.Pro164Leu	missense_variant	3/3
CHST3	XM_047426022.1 linkuse as main transcript	c.491C>T	p.Pro164Leu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHST3	ENST00000373115.5 linkuse as main transcript	c.491C>T	p.Pro164Leu	missense_variant	3/3	1	NM_004273.5	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000423

AC:

AN:

236198

Hom.:

AF XY:

0.00

AC XY:

AN XY:

129766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1451634

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722542

show subpopulations

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:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000344

Hom.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spondyloepiphyseal dysplasia with congenital joint dislocations

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences

This missense variant was found to be pathogenic by various in silico tools, including MutationTaster, SIFT, and PolyPhen. Parents were found to be carriers. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.37

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.87

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.99

MetaSVM

Uncertain

0.67

MutationAssessor

Pathogenic

3.3

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-10

REVEL

Pathogenic

0.87

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.97

MutPred

0.96

Loss of catalytic residue at L161 (P = 0.2472);

MVP

0.97

MPC

1.7

ClinPred

1.0

GERP RS

5.7

Varity_R

0.97

gMVP

0.95

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