NM_175856.5:c.8T>C

Variant names:

• chr5-129904837-T-C
• rs1760174499
• NM_175856.5:c.8T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_175856.5(CHSY3):​c.8T>C​(p.Val3Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000777 in 1,286,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V3G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: CHSY3 NM_175856.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09381896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY3	NM_175856.5	c.8T>C	p.Val3Ala	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.8T>C	p.Val3Ala	missense_variant	Exon 1 of 3	1	NM_175856.5	ENSP00000302629.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.77e-7 AC: 1 AN: 1286754 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 625404

African (AFR) AF: 0.0000375 AC: 1 AN: 26642

American (AMR) AF: 0.00 AC: 0 AN: 26468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20038

East Asian (EAS) AF: 0.00 AC: 0 AN: 31258

South Asian (SAS) AF: 0.00 AC: 0 AN: 66466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1025418

Other (OTH) AF: 0.00 AC: 0 AN: 53442

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	21
DANN	Benign	0.86
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.1
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.028
Sift	Benign	0.30	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.23
MutPred		0.19		Gain of relative solvent accessibility (P = 0.0215);
MVP		0.40
MPC		1.3
ClinPred		0.19	T
GERP RS		2.4
PromoterAI		0.077	Neutral
Varity_R		0.069
gMVP		0.63
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs1760174499; hg19: chr5-129240530;