8-19632487-C-T

Position:

• chr8-19632487-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.-391-30622G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.957 in 152,378 control chromosomes in the GnomAD database, including 69,791 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 0.96 (69791 hom., cov: 35)
• Consequence: CSGALNACT1 NM_001354483.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282

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 (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSGALNACT1	NM_001354483.2	c.-391-30622G>A		intron_variant		ENST00000692225.2	NP_001341412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSGALNACT1	ENST00000692225.2	c.-391-30622G>A		intron_variant			NM_001354483.2	ENSP00000509853.1

Frequencies

GnomAD3 genomes AF: 0.957 AC: 145664 AN: 152260 Hom.: 69725 Cov.: 35

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.950

Gnomad AMR AF: 0.958

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.929

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.954

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

GnomAD4 genome AF: 0.957 AC: 145791 AN: 152378 Hom.: 69791 Cov.: 35 AF XY: 0.956 AC XY: 71223 AN XY: 74516

Gnomad4 AFR AF: 0.985

Gnomad4 AMR AF: 0.958

Gnomad4 ASJ AF: 0.901

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.929

Gnomad4 FIN AF: 0.929

Gnomad4 NFE AF: 0.945

Gnomad4 OTH AF: 0.954

Alfa AF: 0.944 Hom.: 36093

Bravo AF: 0.962

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2975420; hg19: chr8-19489998;