5-129905041-G-T

Variant names:

• chr5-129905041-G-T
• rs780522431
• NM_175856.5:c.212G>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.212G>T​(p.Arg71Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,401,588 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. R71P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CHSY3 NM_175856.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295
• 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=0.08223772).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY3	NM_175856.5	c.212G>T	p.Arg71Leu	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.212G>T	p.Arg71Leu	missense_variant	Exon 1 of 3	1	NM_175856.5	ENSP00000302629.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 150842 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1401588 Hom.: 0 Cov.: 31 AF XY: 0.00000288 AC XY: 2 AN XY: 693582

African (AFR) AF: 0.0000628 AC: 2 AN: 31830

American (AMR) AF: 0.00 AC: 0 AN: 39688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25294

East Asian (EAS) AF: 0.00 AC: 0 AN: 36634

South Asian (SAS) AF: 0.00 AC: 0 AN: 80268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5562

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088322

Other (OTH) AF: 0.00 AC: 0 AN: 58398

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.29
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.038
Sift	Benign	0.082	T
Sift4G	Benign	0.70	T
Polyphen		0.0	B
Vest4		0.19
MutPred		0.25		Gain of stability (P = 0.0182);
MVP		0.24
MPC		1.4
ClinPred		0.072	T
GERP RS		2.1
Varity_R		0.071
gMVP		0.50
Mutation Taster		=89/11	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: rs780522431; hg19: chr5-129240734;