NM_001354483.2:c.-392+75059G>A

Variant names:

• chr8-19682127-C-T
• rs7816924
• NM_001354483.2:c.-392+75059G>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.-392+75059G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 151,998 control chromosomes in the GnomAD database, including 3,268 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 0.19 (3268 hom., cov: 31)
• Consequence: CSGALNACT1 NM_001354483.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470
• Publications: 13 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, ClinGen

CSGALNACT1-AS1 (HGNC:58187):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354483.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSGALNACT1	NM_001354483.2	MANE Select	c.-392+75059G>A		intron	N/A	NP_001341412.1	Q8TDX6-1
	CSGALNACT1	NM_001354475.2		c.-392+32758G>A		intron	N/A	NP_001341404.1	Q8TDX6-1
	CSGALNACT1	NM_001354476.2		c.-392+75723G>A		intron	N/A	NP_001341405.1	Q8TDX6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSGALNACT1	ENST00000692225.2	MANE Select	c.-392+75059G>A		intron	N/A	ENSP00000509853.1	Q8TDX6-1
	CSGALNACT1	ENST00000332246.10	TSL:1	c.-544+346G>A		intron	N/A	ENSP00000330805.6	Q8TDX6-1
	CSGALNACT1	ENST00000695892.1		c.-504+22634G>A		intron	N/A	ENSP00000512242.1	Q8TDX6-1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29451 AN: 151886 Hom.: 3247 Cov.: 31

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.0727

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.128

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.194 AC: 29500 AN: 151998 Hom.: 3268 Cov.: 31 AF XY: 0.193 AC XY: 14314 AN XY: 74284

African (AFR) AF: 0.268 AC: 11096 AN: 41438

American (AMR) AF: 0.204 AC: 3108 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0727 AC: 252 AN: 3468

East Asian (EAS) AF: 0.410 AC: 2112 AN: 5148

South Asian (SAS) AF: 0.197 AC: 950 AN: 4820

European-Finnish (FIN) AF: 0.105 AC: 1110 AN: 10576

Middle Eastern (MID) AF: 0.128 AC: 37 AN: 290

European-Non Finnish (NFE) AF: 0.151 AC: 10280 AN: 67962

Other (OTH) AF: 0.184 AC: 390 AN: 2116

Alfa AF: 0.162 Hom.: 1197

Bravo AF: 0.206

Asia WGS AF: 0.307 AC: 1065 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.99
DANN	Benign	0.37
PhyloP100		-0.47
PromoterAI		-0.0076	Neutral
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: rs7816924; hg19: chr8-19539638;