8-19682751-A-G

Position:

• chr8-19682751-A-G

Variant summary

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

The NM_001354483.2(CSGALNACT1):​c.-392+74435T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 453,790 control chromosomes in the GnomAD database, including 51,880 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 0.47 (17040 hom., cov: 32)
  • Exomes 𝑓: 0.48 (34840 hom.)
• Consequence: CSGALNACT1 NM_001354483.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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]

CSGALNACT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSGALNACT1	NM_001354483.2	c.-392+74435T>C		intron_variant		ENST00000692225.2	NP_001341412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSGALNACT1	ENST00000692225.2	c.-392+74435T>C		intron_variant			NM_001354483.2	ENSP00000509853.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71648 AN: 151942 Hom.: 17023 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.465

GnomAD3 exomes AF: 0.467 AC: 60775 AN: 130262 Hom.: 14399 AF XY: 0.473 AC XY: 33621 AN XY: 71080

Gnomad AFR exome AF: 0.505

Gnomad AMR exome AF: 0.422

Gnomad ASJ exome AF: 0.406

Gnomad EAS exome AF: 0.459

Gnomad SAS exome AF: 0.535

Gnomad FIN exome AF: 0.421

Gnomad NFE exome AF: 0.469

Gnomad OTH exome AF: 0.474

GnomAD4 exome AF: 0.477 AC: 144011 AN: 301734 Hom.: 34840 Cov.: 0 AF XY: 0.484 AC XY: 83207 AN XY: 171966

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.422

Gnomad4 ASJ exome AF: 0.409

Gnomad4 EAS exome AF: 0.463

Gnomad4 SAS exome AF: 0.532

Gnomad4 FIN exome AF: 0.431

Gnomad4 NFE exome AF: 0.475

Gnomad4 OTH exome AF: 0.472

GnomAD4 genome AF: 0.472 AC: 71698 AN: 152056 Hom.: 17040 Cov.: 32 AF XY: 0.468 AC XY: 34765 AN XY: 74302

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.473

Alfa AF: 0.471 Hom.: 18070

Bravo AF: 0.474

Asia WGS AF: 0.498 AC: 1728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11204064; hg19: chr8-19540262;