5-129905109-G-A

Position:

• chr5-129905109-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_175856.5(CHSY3):​c.280G>A​(p.Gly94Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000144 in 1,387,766 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 (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CHSY3 NM_175856.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.59

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21714213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHSY3	NM_175856.5	c.280G>A	p.Gly94Arg	missense_variant	1/3	ENST00000305031.5	NP_787052.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHSY3	ENST00000305031.5	c.280G>A	p.Gly94Arg	missense_variant	1/3	1	NM_175856.5	ENSP00000302629.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1387766 Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1 AN XY: 685654

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000398

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.25e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2023

The c.280G>A (p.G94R) alteration is located in exon 1 (coding exon 1) of the CHSY3 gene. This alteration results from a G to A substitution at nucleotide position 280, causing the glycine (G) at amino acid position 94 to be replaced by an arginine (R). 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	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.67	T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.064
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.015	D
Polyphen		0.98	D
Vest4		0.20
MutPred		0.25		Gain of MoRF binding (P = 0.0235);
MVP		0.59
MPC		2.5
ClinPred		0.78	D
GERP RS		3.1
Varity_R		0.17
gMVP		0.56

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-129240802;