rs74752435

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_014918.5(CHSY1):c.1052A>G(p.Lys351Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 1,614,188 control chromosomes in the GnomAD database, including 358 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 35 hom., cov: 33)

Exomes 𝑓: 0.016 ( 323 hom. )

Consequence

CHSY1
NM_014918.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.31

Publications

9 publications found

Variant links:

Genes affected

CHSY1 (HGNC:17198): (chondroitin sulfate synthase 1) This gene encodes a member of the chondroitin N-acetylgalactosaminyltransferase family. These enzymes possess dual glucuronyltransferase and galactosaminyltransferase activity and play critical roles in the biosynthesis of chondroitin sulfate, a glycosaminoglycan involved in many biological processes including cell proliferation and morphogenesis. Decreased expression of this gene may play a role in colorectal cancer, and mutations in this gene are a cause of temtamy preaxial brachydactyly syndrome. [provided by RefSeq, Dec 2011]

CHSY1 Gene-Disease associations (from GenCC):

temtamy preaxial brachydactyly syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

CHSY1 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 (MetaRNN=0.0014885366).

BP6

Variant 15-101178745-T-C is Benign according to our data. Variant chr15-101178745-T-C is described in ClinVar as Benign. ClinVar VariationId is 466168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY1	NM_014918.5 link	c.1052A>G	p.Lys351Arg	missense_variant	Exon 3 of 3	ENST00000254190.4	NP_055733.2	Q86X52

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHSY1	ENST00000254190.4 link	c.1052A>G	p.Lys351Arg	missense_variant	Exon 3 of 3	1	NM_014918.5	ENSP00000254190.3		Q86X52

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2508

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00591

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0353

Gnomad ASJ

AF:

0.0256

Gnomad EAS

AF:

0.0758

Gnomad SAS

AF:

0.0166

Gnomad FIN

AF:

0.0265

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.0168

GnomAD2 exomes

AF:

0.0250

AC:

6286

AN:

251486

AF XY:

0.0231

show subpopulations

Gnomad AFR exome

AF:

0.00418

Gnomad AMR exome

AF:

0.0558

Gnomad ASJ exome

AF:

0.0317

Gnomad EAS exome

AF:

0.0798

Gnomad FIN exome

AF:

0.0276

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.0235

GnomAD4 exome

AF:

0.0156

AC:

22736

AN:

1461878

Hom.:

323

Cov.:

AF XY:

0.0152

AC XY:

11071

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00418

AC:

140

AN:

33480

American (AMR)

AF:

0.0547

AC:

2445

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0308

AC:

806

AN:

26136

East Asian (EAS)

AF:

0.0650

AC:

2580

AN:

39700

South Asian (SAS)

AF:

0.0125

AC:

1076

AN:

86256

European-Finnish (FIN)

AF:

0.0274

AC:

1462

AN:

53420

Middle Eastern (MID)

AF:

0.0113

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0117

AC:

13034

AN:

1111998

Other (OTH)

AF:

0.0187

AC:

1128

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

1575

3149

4724

6298

7873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

556

1112

1668

2224

2780

<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:

0.0165

AC:

2513

AN:

152310

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1311

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00599

AC:

249

AN:

41568

American (AMR)

AF:

0.0354

AC:

542

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0256

AC:

AN:

3470

East Asian (EAS)

AF:

0.0756

AC:

392

AN:

5186

South Asian (SAS)

AF:

0.0168

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0265

AC:

281

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0123

AC:

837

AN:

68020

Other (OTH)

AF:

0.0175

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

125

250

376

501

626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0151

Hom.:

104

Bravo

AF:

0.0172

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.0112

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0116

AC:

100

ExAC

AF:

0.0215

AC:

2611

Asia WGS

AF:

0.0370

AC:

128

AN:

3478

EpiCase

AF:

0.0131

EpiControl

AF:

0.0113

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 08, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Temtamy preaxial brachydactyly syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.013

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.52

PhyloP100

2.3

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.70

REVEL

Benign

0.047

Sift

Benign

0.40

Sift4G

Benign

0.57

Polyphen

0.0030

Vest4

0.024

MPC

0.26

ClinPred

0.0038

GERP RS

4.5

Varity_R

0.036

gMVP

0.28

Mutation Taster

=91/9

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

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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