chr5-129905308-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_175856.5(CHSY3):​c.479G>C​(p.Gly160Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,504,120 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G160E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000044 (0 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.102068245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY3	NM_175856.5	c.479G>C	p.Gly160Ala	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>C	p.Gly160Ala	missense_variant	Exon 1 of 3	1	NM_175856.5	ENSP00000302629.4

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152094 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000652 AC: 7 AN: 107340 AF XY: 0.0000512

Gnomad AFR exome AF: 0.000164

Gnomad AMR exome AF: 0.000245

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: 0.000306

GnomAD4 exome AF: 0.0000444 AC: 60 AN: 1351918 Hom.: 0 Cov.: 33 AF XY: 0.0000377 AC XY: 25 AN XY: 663764

African (AFR) AF: 0.0000654 AC: 2 AN: 30576

American (AMR) AF: 0.000416 AC: 13 AN: 31248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22480

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 74016

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4952

European-Non Finnish (NFE) AF: 0.0000357 AC: 38 AN: 1063624

Other (OTH) AF: 0.000125 AC: 7 AN: 56184

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152202 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74388

African (AFR) AF: 0.0000962 AC: 4 AN: 41560

American (AMR) AF: 0.00111 AC: 17 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000435 Hom.: 0

Bravo AF: 0.000223

ExAC AF: 0.0000108 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.479G>C (p.G160A) 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 479, causing the glycine (G) at amino acid position 160 to be replaced by an alanine (A). 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	0.089
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.62
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0092	T
Eigen	Benign	0.0094
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.5
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.080
Sift	Benign	0.44	T
Sift4G	Benign	0.57	T
Polyphen		0.44	B
Vest4		0.16
MutPred		0.27		Gain of helix (P = 0.0425);
MVP		0.77
MPC		1.3
ClinPred		0.012	T
GERP RS		3.2
Varity_R		0.073
gMVP		0.32
Mutation Taster		=82/18	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;