8-19632487-C-T

Variant names:

• chr8-19632487-C-T
• rs2975420
• NM_001354483.2:c.-391-30622G>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.-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
• Publications: 4 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

ACMG classification

Our verdict: Benign. The variant received -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.

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.-391-30622G>A		intron	N/A	NP_001341412.1	Q8TDX6-1
	CSGALNACT1	NM_001354475.2		c.-391-30622G>A		intron	N/A	NP_001341404.1	Q8TDX6-1
	CSGALNACT1	NM_001354476.2		c.-391-30622G>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.-391-30622G>A		intron	N/A	ENSP00000509853.1	Q8TDX6-1
	CSGALNACT1	ENST00000332246.10	TSL:1	c.-543-30622G>A		intron	N/A	ENSP00000330805.6	Q8TDX6-1
	CSGALNACT1	ENST00000695892.1		c.-503-7234G>A		intron	N/A	ENSP00000512242.1	Q8TDX6-1

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

African (AFR) AF: 0.985 AC: 40987 AN: 41598

American (AMR) AF: 0.958 AC: 14659 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3128 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5182 AN: 5190

South Asian (SAS) AF: 0.929 AC: 4483 AN: 4828

European-Finnish (FIN) AF: 0.929 AC: 9867 AN: 10626

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.945 AC: 64324 AN: 68038

Other (OTH) AF: 0.954 AC: 2019 AN: 2116

Alfa AF: 0.946 Hom.: 50965

Bravo AF: 0.962

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.67
PhyloP100		0.28
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: rs2975420; hg19: chr8-19489998;