rs17128525

Variant names:

• chr8-19506495-C-T
• rs17128525
• NM_001354483.2:c.-296-365G>A

Variant summary

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

The NM_001354483.2(CSGALNACT1):​c.-296-365G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,110 control chromosomes in the GnomAD database, including 13,847 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 0.42 (13847 hom., cov: 32)
• Consequence: CSGALNACT1 NM_001354483.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSGALNACT1	NM_001354483.2	c.-296-365G>A		intron_variant	Intron 2 of 8	ENST00000692225.2	NP_001341412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSGALNACT1	ENST00000692225.2	c.-296-365G>A		intron_variant	Intron 2 of 8		NM_001354483.2	ENSP00000509853.1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63182 AN: 151992 Hom.: 13813 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.416 AC: 63262 AN: 152110 Hom.: 13847 Cov.: 32 AF XY: 0.413 AC XY: 30729 AN XY: 74364

African (AFR) AF: 0.555 AC: 23014 AN: 41470

American (AMR) AF: 0.314 AC: 4797 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1232 AN: 3468

East Asian (EAS) AF: 0.163 AC: 844 AN: 5182

South Asian (SAS) AF: 0.465 AC: 2242 AN: 4820

European-Finnish (FIN) AF: 0.346 AC: 3660 AN: 10566

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26155 AN: 67990

Other (OTH) AF: 0.357 AC: 753 AN: 2110

Alfa AF: 0.399 Hom.: 6881

Bravo AF: 0.414

Asia WGS AF: 0.314 AC: 1094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0030
DANN	Benign	0.68
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17128525; hg19: chr8-19364006;