rs4148941

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004273.5(CHST3):c.*763C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 152,052 control chromosomes in the GnomAD database, including 34,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 34216 hom., cov: 32)

Exomes 𝑓: 0.58 ( 7 hom. )

Consequence

CHST3
NM_004273.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.23

Publications

24 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 10-72009234-C-A is Benign according to our data. Variant chr10-72009234-C-A is described in ClinVar as Benign. ClinVar VariationId is 300581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
CHST3	NM_004273.5 link	c.*763C>A	3_prime_UTR_variant	Exon 3 of 3	ENST00000373115.5	NP_004264.2
CHST3	NM_001441201.1 link	c.*763C>A	3_prime_UTR_variant	Exon 3 of 3		NP_001428130.1
CHST3	NM_001441202.1 link	c.*763C>A	3_prime_UTR_variant	Exon 3 of 3		NP_001428131.1
CHST3	XM_011540369.3 link	c.*763C>A	3_prime_UTR_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.*763C>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_004273.5	ENSP00000362207.4

Frequencies

GnomAD3 genomes

AF:

0.657

AC:

99766

AN:

151898

Hom.:

34167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.870

Gnomad AMI

AF:

0.561

Gnomad AMR

AF:

0.617

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.407

Gnomad SAS

AF:

0.510

Gnomad FIN

AF:

0.533

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.594

Gnomad OTH

AF:

0.649

GnomAD4 exome

AF:

0.583

AC:

AN:

Hom.:

Cov.:

AF XY:

0.545

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.600

AC:

AN:

Other (OTH)

AF:

0.700

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.657

AC:

99869

AN:

152016

Hom.:

34216

Cov.:

AF XY:

0.647

AC XY:

48037

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.870

AC:

36095

AN:

41470

American (AMR)

AF:

0.617

AC:

9415

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

1736

AN:

3470

East Asian (EAS)

AF:

0.407

AC:

2103

AN:

5162

South Asian (SAS)

AF:

0.509

AC:

2454

AN:

4820

European-Finnish (FIN)

AF:

0.533

AC:

5614

AN:

10538

Middle Eastern (MID)

AF:

0.585

AC:

172

AN:

294

European-Non Finnish (NFE)

AF:

0.594

AC:

40404

AN:

67968

Other (OTH)

AF:

0.646

AC:

1367

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1649

3298

4947

6596

8245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

780

1560

2340

3120

3900

<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:

0.616

Hom.:

93995

Bravo

AF:

0.674

Asia WGS

AF:

0.501

AC:

1745

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spondyloepiphyseal dysplasia with congenital joint dislocations

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Skeletal dysplasia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Spondyloepiphyseal dysplasia congenita

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Larsen syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.052

(source)

DANN

Benign

0.49

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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