rs32225

Variant names:

• chr5-129914784-G-C
• rs32225
• NM_175856.5:c.1086+6424G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175856.5(CHSY3):​c.1086+6424G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,068 control chromosomes in the GnomAD database, including 12,394 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12394 hom., cov: 33)
• Consequence: CHSY3 NM_175856.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY3	NM_175856.5	c.1086+6424G>C		intron_variant	Intron 2 of 2	ENST00000305031.5	NP_787052.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHSY3	ENST00000305031.5	c.1086+6424G>C		intron_variant	Intron 2 of 2	1	NM_175856.5	ENSP00000302629.4
CHSY3	ENST00000507545.1	n.274+6424G>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60863 AN: 151952 Hom.: 12368 Cov.: 33

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.391

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.401 AC: 60928 AN: 152068 Hom.: 12394 Cov.: 33 AF XY: 0.407 AC XY: 30243 AN XY: 74342

African (AFR) AF: 0.461 AC: 19129 AN: 41484

American (AMR) AF: 0.413 AC: 6307 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1117 AN: 3470

East Asian (EAS) AF: 0.407 AC: 2108 AN: 5174

South Asian (SAS) AF: 0.457 AC: 2206 AN: 4828

European-Finnish (FIN) AF: 0.439 AC: 4634 AN: 10560

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.356 AC: 24195 AN: 67958

Other (OTH) AF: 0.391 AC: 825 AN: 2112

Alfa AF: 0.382 Hom.: 1406

Bravo AF: 0.400

Asia WGS AF: 0.459 AC: 1595 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.57
PhyloP100		0.018
Mutation Taster		=100/0	polymorphism (auto)

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: rs32225; hg19: chr5-129250477; COSMIC: COSV59274260;