5-129905503-C-T

Variant names:

• chr5-129905503-C-T
• rs1760246661
• NM_175856.5:c.674C>T

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.674C>T​(p.Ala225Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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. A225G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHSY3 NM_175856.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• 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]

CHSY3-AS1 (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=0.14730954).

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.674C>T	p.Ala225Val	missense	Exon 1 of 3	NP_787052.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHSY3	ENST00000305031.5	TSL:1 MANE Select	c.674C>T	p.Ala225Val	missense	Exon 1 of 3	ENSP00000302629.4	Q70JA7
	CHSY3-AS1	ENST00000503616.5	TSL:3	n.72+343G>A		intron	N/A
	CHSY3-AS1	ENST00000515569.1	TSL:2	n.82+77G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.3
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.073
Sift	Benign	0.13	T
Sift4G	Benign	0.28	T
Polyphen		0.95	P
Vest4		0.28
MutPred		0.31		Gain of helix (P = 0.062)
MVP		0.53
MPC		1.2
ClinPred		0.63	D
GERP RS		1.4
Varity_R		0.11
gMVP		0.31
Mutation Taster		=81/19	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: rs1760246661; hg19: chr5-129241196; COSMIC: COSV100519733; COSMIC: COSV100519733;