Genetic Variant CHSY3:p.Gly160Glu (chr5-129905308-G-A) – 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.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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G160A) has been classified 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

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:

CHSY3-AS1 (HGNC:58253):

CHSY3-AS1 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=0.019097567).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175856.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHSY3	NM_175856.5	MANE Select	c.479G>A	p.Gly160Glu	missense	Exon 1 of 3	NP_787052.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHSY3	ENST00000305031.5	TSL:1 MANE Select	c.479G>A	p.Gly160Glu	missense	Exon 1 of 3	ENSP00000302629.4	Q70JA7
CHSY3-AS1	ENST00000503616.5	TSL:3	n.72+538C>T		intron	N/A
CHSY3-AS1	ENST00000515569.1	TSL:2	n.82+272C>T		intron	N/A

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

GnomAD2 exomes

AF:

0.000326

AC:

AN:

107340

AF XY:

0.000273

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 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

African (AFR)

AF:

0.00124

AC:

AN:

30576

American (AMR)

AF:

0.000736

AC:

AN:

31248

Ashkenazi Jewish (ASJ)

AF:

0.000445

AC:

AN:

22478

East Asian (EAS)

AF:

0.00

AC:

AN:

35578

South Asian (SAS)

AF:

0.0000270

AC:

AN:

74016

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33260

Middle Eastern (MID)

AF:

0.00222

AC:

AN:

4952

European-Non Finnish (NFE)

AF:

0.000137

AC:

146

AN:

1063624

Other (OTH)

AF:

0.000498

AC:

AN:

56184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000532

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000565

AC XY:

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.00130

AC:

AN:

41560

American (AMR)

AF:

0.000392

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5118

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

67994

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.000589

ExAC

AF:

0.000193

AC:

Asia WGS

AF:

0.000290

AC:

AN:

3464

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

(source)

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

PhyloP100

1.5

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

Mutation Taster

=83/17

polymorphism

(source)

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over