NM_014918.5:c.57C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014918.5(CHSY1):c.57C>T(p.Gly19Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,161,700 control chromosomes in the GnomAD database, including 17,740 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4917 hom., cov: 31)

Exomes 𝑓: 0.15 ( 12823 hom. )

Consequence

CHSY1
NM_014918.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.108

Publications

4 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 15-101251400-G-A is Benign according to our data. Variant chr15-101251400-G-A is described in ClinVar as Benign. ClinVar VariationId is 585675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.108 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY1	NM_014918.5 link	c.57C>T	p.Gly19Gly	synonymous_variant	Exon 1 of 3	ENST00000254190.4	NP_055733.2	Q86X52
CHSY1	XM_011521364.3 link	c.57C>T	p.Gly19Gly	synonymous_variant	Exon 1 of 4		XP_011519666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHSY1	ENST00000254190.4 link	c.57C>T	p.Gly19Gly	synonymous_variant	Exon 1 of 3	1	NM_014918.5	ENSP00000254190.3		Q86X52

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

32760

AN:

145686

Hom.:

4919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.188

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.0150

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.261

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.237

GnomAD2 exomes

AF:

0.139

AC:

9752

AN:

70160

AF XY:

0.142

show subpopulations

Gnomad AFR exome

AF:

0.466

Gnomad AMR exome

AF:

0.0981

Gnomad ASJ exome

AF:

0.172

Gnomad EAS exome

AF:

0.0193

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.156

GnomAD4 exome

AF:

0.151

AC:

152990

AN:

1015934

Hom.:

12823

Cov.:

AF XY:

0.149

AC XY:

74344

AN XY:

497420

show subpopulations

African (AFR)

AF:

0.439

AC:

8539

AN:

19456

American (AMR)

AF:

0.108

AC:

1868

AN:

17258

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

2126

AN:

12686

East Asian (EAS)

AF:

0.0181

AC:

AN:

5460

South Asian (SAS)

AF:

0.138

AC:

7871

AN:

57052

European-Finnish (FIN)

AF:

0.103

AC:

925

AN:

8964

Middle Eastern (MID)

AF:

0.229

AC:

530

AN:

2312

European-Non Finnish (NFE)

AF:

0.146

AC:

125351

AN:

857754

Other (OTH)

AF:

0.162

AC:

5681

AN:

34992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

5829

11658

17487

23316

29145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5616

11232

16848

22464

28080

<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:

0.225

AC:

32774

AN:

145766

Hom.:

4917

Cov.:

AF XY:

0.221

AC XY:

15683

AN XY:

70916

show subpopulations

African (AFR)

AF:

0.424

AC:

17182

AN:

40488

American (AMR)

AF:

0.188

AC:

2772

AN:

14738

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

531

AN:

3378

East Asian (EAS)

AF:

0.0151

AC:

AN:

5042

South Asian (SAS)

AF:

0.144

AC:

689

AN:

4794

European-Finnish (FIN)

AF:

0.105

AC:

885

AN:

8414

Middle Eastern (MID)

AF:

0.259

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.151

AC:

9898

AN:

65702

Other (OTH)

AF:

0.234

AC:

472

AN:

2020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1094

2188

3281

4375

5469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.209

Hom.:

949

Bravo

AF:

0.238

Asia WGS

AF:

0.0930

AC:

242

AN:

2622

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 10, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

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

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

PhyloP100

0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Mutation Taster

=99/1

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