Variant 5-129905308-G-A 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.479G>A(p.Gly160Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000225 in 1,504,118 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

CHSY3
NM_175856.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.53

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:

(HGNC:):

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=0.019097567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHSY3	NM_175856.5 linkuse as main transcript	c.479G>A	p.Gly160Glu	missense_variant	1/3	ENST00000305031.5	NP_787052.3
LOC112267944	XR_002956248.2 linkuse as main transcript	n.86+534C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHSY3	ENST00000305031.5 linkuse as main transcript	c.479G>A	p.Gly160Glu	missense_variant	1/3	1	NM_175856.5	ENSP00000302629	P1
	ENST00000503616.5 linkuse as main transcript	n.72+538C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000533

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000326

AC:

AN:

107340

Hom.:

AF XY:

0.000273

AC XY:

AN XY:

58596

show subpopulations

Gnomad AFR exome

AF:

0.00131

Gnomad AMR exome

AF:

0.000637

Gnomad ASJ exome

AF:

0.000577

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000584

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000171

Gnomad OTH exome

AF:

0.000917

GnomAD4 exome

AF:

0.000191

AC:

258

AN:

1351916

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

115

AN XY:

663762

show subpopulations

Gnomad4 AFR exome

AF:

0.00124

Gnomad4 AMR exome

AF:

0.000736

Gnomad4 ASJ exome

AF:

0.000445

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000270

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000137

Gnomad4 OTH exome

AF:

0.000498

GnomAD4 genome

AF:

0.000532

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000565

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00284

Bravo

AF:

0.000589

ExAC

AF:

0.000193

AC:

Asia WGS

AF:

0.000290

AC:

AN:

3464

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

Feb 10, 2022

The c.479G>A (p.G160E) alteration is located in exon 1 (coding exon 1) of the CHSY3 gene. This alteration results from a G to A substitution at nucleotide position 479, causing the glycine (G) at amino acid position 160 to be replaced by a glutamic acid (E). 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

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0075

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.58

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

MutationTaster

Benign

0.63

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.49

REVEL

Benign

0.085

Sift

Benign

0.20

Sift4G

Benign

0.36

Polyphen

0.84

Vest4

0.16

MutPred

0.36

Gain of solvent accessibility (P = 9e-04);

MVP

0.81

MPC

1.7

ClinPred

0.016

GERP RS

3.2

Varity_R

0.088

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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