Genetic Variant CHSY3:p.Asn155Lys (chr5-129905294-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_175856.5(CHSY3):c.465C>A(p.Asn155Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000977 in 1,330,514 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000098 ( 0 hom. )

Consequence

CHSY3
NM_175856.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.163

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: Uncertain_significance. The variant received 2 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity CHSS3_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14208406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY3	NM_175856.5 link	c.465C>A	p.Asn155Lys	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.465C>A	p.Asn155Lys	missense_variant	Exon 1 of 3	1	NM_175856.5	ENSP00000302629.4		Q70JA7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

93598

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000977

AC:

AN:

1330514

Hom.:

Cov.:

AF XY:

0.00000766

AC XY:

AN XY:

652320

show subpopulations

African (AFR)

AF:

0.0000333

AC:

AN:

30014

American (AMR)

AF:

0.00

AC:

AN:

29540

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21338

East Asian (EAS)

AF:

0.00

AC:

AN:

35234

South Asian (SAS)

AF:

0.00

AC:

AN:

71106

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32100

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4794

European-Non Finnish (NFE)

AF:

0.0000114

AC:

AN:

1050952

Other (OTH)

AF:

0.00

AC:

AN:

55436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 30, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.465C>A (p.N155K) alteration is located in exon 1 (coding exon 1) of the CHSY3 gene. This alteration results from a C to A substitution at nucleotide position 465, causing the asparagine (N) at amino acid position 155 to be replaced by a lysine (K). 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

0.27

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.56

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.16

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.4

REVEL

Benign

0.012

Sift

Benign

0.23

Sift4G

Benign

0.46

Polyphen

0.25

Vest4

0.20

MutPred

0.32

Gain of ubiquitination at N155 (P = 0.0042);

MVP

0.69

MPC

2.3

ClinPred

0.87

GERP RS

3.3

Varity_R

0.11

gMVP

0.29

Mutation Taster

=59/41

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

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

chr5-129905294-C-A

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