rs32225

chr5-129914784-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CHSY3	NM_175856.5	c.1086+6424G>C		intron_variant		ENST00000305031.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHSY3	ENST00000305031.5	c.1086+6424G>C		intron_variant		1	NM_175856.5	P1
CHSY3	ENST00000507545.1	n.274+6424G>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.391

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

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

LitVar

Other links and lift over

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