5-129905266-G-T

Variant names:

• chr5-129905266-G-T
• rs925007820
• NM_175856.5:c.437G>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.437G>T​(p.Arg146Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,303,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. R146T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CHSY3 NM_175856.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415
• 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=0.08979645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY3	NM_175856.5	c.437G>T	p.Arg146Ile	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.437G>T	p.Arg146Ile	missense_variant	Exon 1 of 3	1	NM_175856.5	ENSP00000302629.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000153 AC: 2 AN: 1303298 Hom.: 0 Cov.: 31 AF XY: 0.00000157 AC XY: 1 AN XY: 637596

African (AFR) AF: 0.00 AC: 0 AN: 27920

American (AMR) AF: 0.00 AC: 0 AN: 25412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19862

East Asian (EAS) AF: 0.00 AC: 0 AN: 33986

South Asian (SAS) AF: 0.0000149 AC: 1 AN: 66984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31052

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4430

European-Non Finnish (NFE) AF: 9.62e-7 AC: 1 AN: 1039328

Other (OTH) AF: 0.00 AC: 0 AN: 54324

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.41
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.024
Sift	Benign	0.037	D
Sift4G	Uncertain	0.045	D
Polyphen		0.0	B
Vest4		0.24
MutPred		0.38		Gain of methylation at R149 (P = 0.079);
MVP		0.36
MPC		1.8
ClinPred		0.079	T
GERP RS		-0.66
Varity_R		0.074
gMVP		0.46
Mutation Taster		=92/8	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: rs925007820; hg19: chr5-129240959;