rs535309495

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_004273.5(CHST3):c.959C>G(p.Thr320Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,549,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T320T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

CHST3
NM_004273.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.302

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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066131055).

BP6

Variant 10-72007990-C-G is Benign according to our data. Variant chr10-72007990-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 533430.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000696 (106/152306) while in subpopulation AFR AF = 0.00243 (101/41576). AF 95% confidence interval is 0.00204. There are 0 homozygotes in GnomAd4. There are 45 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CHST3	NM_004273.5 link	c.959C>G	p.Thr320Ser	missense_variant	Exon 3 of 3	ENST00000373115.5	NP_004264.2
CHST3	NM_001441201.1 link	c.959C>G	p.Thr320Ser	missense_variant	Exon 3 of 3		NP_001428130.1
CHST3	NM_001441202.1 link	c.959C>G	p.Thr320Ser	missense_variant	Exon 3 of 3		NP_001428131.1
CHST3	XM_011540369.3 link	c.959C>G	p.Thr320Ser	missense_variant	Exon 3 of 3		XP_011538671.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST3	ENST00000373115.5 link	c.959C>G	p.Thr320Ser	missense_variant	Exon 3 of 3	1	NM_004273.5	ENSP00000362207.4

Frequencies

GnomAD3 genomes

AF:

0.000697

AC:

106

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000478

GnomAD2 exomes

AF:

0.000155

AC:

AN:

148336

AF XY:

0.000138

show subpopulations

Gnomad AFR exome

AF:

0.00237

Gnomad AMR exome

AF:

0.000163

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000751

AC:

105

AN:

1397262

Hom.:

Cov.:

AF XY:

0.0000624

AC XY:

AN XY:

689172

show subpopulations

African (AFR)

AF:

0.00263

AC:

AN:

31562

American (AMR)

AF:

0.000140

AC:

AN:

35676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25142

East Asian (EAS)

AF:

0.00

AC:

AN:

35714

South Asian (SAS)

AF:

0.00

AC:

AN:

79226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47934

Middle Eastern (MID)

AF:

0.000359

AC:

AN:

5566

European-Non Finnish (NFE)

AF:

0.00000464

AC:

AN:

1078506

Other (OTH)

AF:

0.000173

AC:

AN:

57936

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

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000696

AC:

106

AN:

152306

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00243

AC:

101

AN:

41576

American (AMR)

AF:

0.000261

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.000729

ExAC

AF:

0.000167

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3470

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spondyloepiphyseal dysplasia with congenital joint dislocations

Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.8

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.12

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.52

M_CAP

Benign

0.0091

MetaRNN

Benign

0.0066

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.010

PhyloP100

-0.30

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.72

REVEL

Benign

0.18

Sift

Benign

0.75

Sift4G

Benign

0.87

Polyphen

0.0

Vest4

0.023

MutPred

0.42

Gain of disorder (P = 0.0655);

MVP

0.77

MPC

0.59

ClinPred

0.0016

GERP RS

-0.039

Varity_R

0.054

gMVP

0.57

Mutation Taster

=99/1

polymorphism

(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

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over