5-129904864-T-C

Variant names:

• chr5-129904864-T-C
• rs1012598884
• NM_175856.5:c.35T>C

Variant summary

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

The NM_175856.5(CHSY3):​c.35T>C​(p.Val12Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000833 in 1,320,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: CHSY3 NM_175856.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.14
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.35T>C	p.Val12Ala	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.35T>C	p.Val12Ala	missense	Exon 1 of 3	ENSP00000302629.4	Q70JA7
	CHSY3-AS1	ENST00000503616.5	TSL:3	n.72+982A>G		intron	N/A
	CHSY3-AS1	ENST00000515569.1	TSL:2	n.82+716A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000833 AC: 11 AN: 1320880 Hom.: 0 Cov.: 31 AF XY: 0.00000931 AC XY: 6 AN XY: 644778

African (AFR) AF: 0.00 AC: 0 AN: 27592

American (AMR) AF: 0.00 AC: 0 AN: 30252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22428

East Asian (EAS) AF: 0.00 AC: 0 AN: 32184

South Asian (SAS) AF: 0.00 AC: 0 AN: 73020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.0000106 AC: 11 AN: 1039990

Other (OTH) AF: 0.00 AC: 0 AN: 54752

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.68	T
M_CAP	Pathogenic	0.74	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.1	L
PhyloP100		5.1
PrimateAI	Pathogenic	0.97	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.014	D
Polyphen		0.99	D
Vest4		0.48
MutPred		0.30		Gain of helix (P = 0.0425)
MVP		0.76
MPC		2.0
ClinPred		0.83	D
GERP RS		2.4
PromoterAI		-0.010	Neutral
Varity_R		0.24
gMVP		0.80
Mutation Taster		=58/42	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: rs1012598884; hg19: chr5-129240557;