8-19682611-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001354483.2(CSGALNACT1):c.-392+74575G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 453,750 control chromosomes in the GnomAD database, including 10,794 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 0.22 (3967 hom., cov: 31)
  • Exomes 𝑓: 0.20 (6827 hom.)
• Consequence: CSGALNACT1 NM_001354483.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

Genes affected

CSGALNACT1 (HGNC:24290): (chondroitin sulfate N-acetylgalactosaminyltransferase 1) This gene encodes an enzyme that transfers N-acetylglucosamine (GalNAc) to the core tetrasaccharide linker and to elongating chondroitin sulfate chains in proteoglycans. Knockout of the orthologous mouse gene indicates that the protein is necessary for normal cartilage development and aggrecan metabolism. Mutations in this gene are associated with multiple sclerosis progression, and with mild skeletal dysplasia and joint laxity. [provided by RefSeq, Aug 2017]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSGALNACT1	NM_001354483.2	c.-392+74575G>A		intron_variant		ENST00000692225.2
LOC124901899	XR_007060841.1	n.283+3784C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSGALNACT1	ENST00000692225.2	c.-392+74575G>A		intron_variant			NM_001354483.2	P1
	ENST00000519803.1	n.256+3784C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33316 AN: 151906 Hom.: 3944 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.198

GnomAD4 exome AF: 0.203 AC: 61382 AN: 301730 Hom.: 6827 Cov.: 0 AF XY: 0.205 AC XY: 35228 AN XY: 171974

Gnomad4 AFR exome AF: 0.288

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.429

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.199

GnomAD4 genome AF: 0.220 AC: 33372 AN: 152020 Hom.: 3967 Cov.: 31 AF XY: 0.219 AC XY: 16271 AN XY: 74320

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.208

Alfa AF: 0.187 Hom.: 5813

Bravo AF: 0.229

Asia WGS AF: 0.328 AC: 1139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.13
Dann	Benign	0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11985450; hg19: chr8-19540122;