rs535233532

Variant names:

• chr5-129905308-G-A
• rs535233532
• NM_175856.5:c.479G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-129905308-G-A
• chr5-129905308-G-C
• chr5-129905308-G-T

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.53
• Publications: 0 publications found

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]

ENSG00000251680 (HGNC:58253):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.019097567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY3	NM_175856.5	c.479G>A	p.Gly160Glu	missense_variant	Exon 1 of 3	ENST00000305031.5	NP_787052.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHSY3	ENST00000305031.5	c.479G>A	p.Gly160Glu	missense_variant	Exon 1 of 3	1	NM_175856.5	ENSP00000302629.4

Frequencies

GnomAD3 genomes AF: 0.000533 AC: 81 AN: 152094 Hom.: 0 Cov.: 33

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: 35 AN: 107340 AF XY: 0.000273

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.: 1 Cov.: 33 AF XY: 0.000173 AC XY: 115 AN XY: 663762

African (AFR) AF: 0.00124 AC: 38 AN: 30576

American (AMR) AF: 0.000736 AC: 23 AN: 31248

Ashkenazi Jewish (ASJ) AF: 0.000445 AC: 10 AN: 22478

East Asian (EAS) AF: 0.00 AC: 0 AN: 35578

South Asian (SAS) AF: 0.0000270 AC: 2 AN: 74016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33260

Middle Eastern (MID) AF: 0.00222 AC: 11 AN: 4952

European-Non Finnish (NFE) AF: 0.000137 AC: 146 AN: 1063624

Other (OTH) AF: 0.000498 AC: 28 AN: 56184

GnomAD4 genome AF: 0.000532 AC: 81 AN: 152202 Hom.: 0 Cov.: 33 AF XY: 0.000565 AC XY: 42 AN XY: 74388

African (AFR) AF: 0.00130 AC: 54 AN: 41560

American (AMR) AF: 0.000392 AC: 6 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67994

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000589

ExAC AF: 0.000193 AC: 18

Asia WGS AF: 0.000290 AC: 1 AN: 3464

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0075	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.5
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.49	N
REVEL	Benign	0.085
Sift	Benign	0.20	T
Sift4G	Benign	0.36	T
Polyphen		0.84	P
Vest4		0.16
MutPred		0.36		Gain of solvent accessibility (P = 9e-04);
MVP		0.81
MPC		1.7
ClinPred		0.016	T
GERP RS		3.2
Varity_R		0.088
gMVP		0.34
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs535233532; hg19: chr5-129241001;