rs1554817549

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1PM2

The NM_004273.5(CHST3):c.680C>G(p.Ser227Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,454,202 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S227S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CHST3
NM_004273.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.84

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

spondyloepiphyseal dysplasia with congenital joint dislocations
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

CHST3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM1

In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 5 uncertain in NM_004273.5

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST3	NM_004273.5 link	c.680C>G	p.Ser227Cys	missense_variant	Exon 3 of 3	ENST00000373115.5	NP_004264.2	Q7LGC8
CHST3	NM_001441201.1 link	c.680C>G	p.Ser227Cys	missense_variant	Exon 3 of 3		NP_001428130.1
CHST3	NM_001441202.1 link	c.680C>G	p.Ser227Cys	missense_variant	Exon 3 of 3		NP_001428131.1
CHST3	XM_011540369.3 link	c.680C>G	p.Ser227Cys	missense_variant	Exon 3 of 3		XP_011538671.1	Q7LGC8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST3	ENST00000373115.5 link	c.680C>G	p.Ser227Cys	missense_variant	Exon 3 of 3	1	NM_004273.5	ENSP00000362207.4		Q7LGC8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454202

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723764

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.00

AC:

AN:

86160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46510

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111686

Other (OTH)

AF:

0.00

AC:

AN:

60244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Jun 21, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.680C>G (p.S227C) alteration is located in exon 3 (coding exon 2) of the CHST3 gene. This alteration results from a C to G substitution at nucleotide position 680, causing the serine (S) at amino acid position 227 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Spondyloepiphyseal dysplasia with congenital joint dislocations

Uncertain:1

May 03, 2020

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.24

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.82

M_CAP

Pathogenic

0.32

MetaRNN

Uncertain

0.60

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.5

PhyloP100

4.8

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.9

REVEL

Pathogenic

0.77

Sift

Uncertain

0.016

Sift4G

Benign

0.064

Polyphen

1.0

Vest4

0.19

MutPred

0.68

Loss of disorder (P = 0.0081);

MVP

0.99

MPC

1.6

ClinPred

0.96

GERP RS

5.7

Varity_R

0.47

gMVP

0.82

Mutation Taster

=42/58

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over