Genetic Variant CHSY3:p.Gly94Val (chr5-129905110-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_175856.5(CHSY3):c.281G>T(p.Gly94Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000937 in 1,387,852 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G94E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000094 ( 1 hom. )

Consequence

CHSY3
NM_175856.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.528

Publications

0 publications found

Variant links:

Genes affected

CHSY3 (HGNC:24293): (chondroitin sulfate synthase 3) CSS3 is a glycosyltransferase that has both glucuronyltransferase and N-acetylgalactosaminyltransferase activities (Yada et al., 2003 [PubMed 12907687]).[supplied by OMIM, Mar 2008]

CHSY3 links:

ENSG00000251680 (HGNC:58253):

ENSG00000251680 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0355646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY3	NM_175856.5 link	c.281G>T	p.Gly94Val	missense_variant	Exon 1 of 3	ENST00000305031.5	NP_787052.3	Q70JA7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHSY3	ENST00000305031.5 link	c.281G>T	p.Gly94Val	missense_variant	Exon 1 of 3	1	NM_175856.5	ENSP00000302629.4		Q70JA7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000522

AC:

AN:

134050

AF XY:

0.0000405

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000394

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000550

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000937

AC:

AN:

1387852

Hom.:

Cov.:

AF XY:

0.00000729

AC XY:

AN XY:

685698

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31394

American (AMR)

AF:

0.0000270

AC:

AN:

37088

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25148

East Asian (EAS)

AF:

0.000334

AC:

AN:

35896

South Asian (SAS)

AF:

0.00

AC:

AN:

79254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34438

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5566

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1081084

Other (OTH)

AF:

0.00

AC:

AN:

57984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000384

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000295

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 15, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.281G>T (p.G94V) alteration is located in exon 1 (coding exon 1) of the CHSY3 gene. This alteration results from a G to T substitution at nucleotide position 281, causing the glycine (G) at amino acid position 94 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.60

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

0.53

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.30

REVEL

Benign

0.10

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.029

Polyphen

0.95

Vest4

0.33

MutPred

0.27

Loss of relative solvent accessibility (P = 0.0071);

MVP

0.67

MPC

2.5

ClinPred

0.13

GERP RS

3.1

Varity_R

0.12

gMVP

0.60

Mutation Taster

=81/19

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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chr5-129905110-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over