Variant 5-129904974-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_175856.5(CHSY3):c.145G>C(p.Gly49Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,567,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

CHSY3
NM_175856.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.618

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:

LOC112267944 (HGNC:):

LOC112267944 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.021833718).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHSY3	NM_175856.5 link	c.145G>C	p.Gly49Arg	missense_variant	1/3	ENST00000305031.5	NP_787052.3	Q70JA7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHSY3	ENST00000305031.5 link	c.145G>C	p.Gly49Arg	missense_variant	1/3	1	NM_175856.5	ENSP00000302629.4		Q70JA7

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00135

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000420

AC:

AN:

173696

Hom.:

AF XY:

0.000500

AC XY:

AN XY:

96060

show subpopulations

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 SAS exome

AF:

0.0000401

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000969

Gnomad OTH exome

AF:

0.000215

GnomAD4 exome

AF:

0.00112

AC:

1582

AN:

1414982

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

772

AN XY:

701012

show subpopulations

Gnomad4 AFR exome

AF:

0.000186

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.000103

Gnomad4 NFE exome

AF:

0.00138

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.000663

AC:

101

AN:

152288

Hom.:

Cov.:

AF XY:

0.000577

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00135

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000903

Hom.:

Bravo

AF:

0.000563

ExAC

AF:

0.000286

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3472

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 05, 2024

The c.145G>C (p.G49R) alteration is located in exon 1 (coding exon 1) of the CHSY3 gene. This alteration results from a G to C substitution at nucleotide position 145, causing the glycine (G) at amino acid position 49 to be replaced by an arginine (R). 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

0.31

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0098

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.70

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.022

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.51

REVEL

Benign

0.060

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.016

Polyphen

0.0

Vest4

0.34

MVP

0.55

MPC

2.5

ClinPred

0.21

GERP RS

3.0

Varity_R

0.076

gMVP

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over