NM_001354483.2:c.-391-71587A>G

Variant names:

• chr8-19673452-T-C
• rs923768
• NM_001354483.2:c.-391-71587A>G

Variant summary

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

The NM_001354483.2(CSGALNACT1):​c.-391-71587A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,108 control chromosomes in the GnomAD database, including 16,526 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 0.46 (16526 hom., cov: 33)
• Consequence: CSGALNACT1 NM_001354483.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• skeletal dysplasia, mild, with joint laxity and advanced bone age

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSGALNACT1	NM_001354483.2	c.-391-71587A>G		intron_variant	Intron 1 of 8	ENST00000692225.2	NP_001341412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSGALNACT1	ENST00000692225.2	c.-391-71587A>G		intron_variant	Intron 1 of 8		NM_001354483.2	ENSP00000509853.1

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69731 AN: 151990 Hom.: 16522 Cov.: 33

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.459 AC: 69758 AN: 152108 Hom.: 16526 Cov.: 33 AF XY: 0.454 AC XY: 33783 AN XY: 74352

African (AFR) AF: 0.349 AC: 14486 AN: 41494

American (AMR) AF: 0.447 AC: 6831 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1778 AN: 3470

East Asian (EAS) AF: 0.395 AC: 2040 AN: 5166

South Asian (SAS) AF: 0.542 AC: 2615 AN: 4828

European-Finnish (FIN) AF: 0.439 AC: 4638 AN: 10576

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35567 AN: 67970

Other (OTH) AF: 0.495 AC: 1047 AN: 2116

Alfa AF: 0.511 Hom.: 33473

Bravo AF: 0.452

Asia WGS AF: 0.488 AC: 1697 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	0.30
DANN	Benign	0.54
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs923768; hg19: chr8-19530963;