8-19682751-A-T

Variant names:

• chr8-19682751-A-T
• rs11204064
• NM_001354483.2:c.-392+74435T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001354483.2(CSGALNACT1):​c.-392+74435T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 301,762 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: CSGALNACT1 NM_001354483.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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+74435T>A		intron	N/A	NP_001341412.1	Q8TDX6-1
	CSGALNACT1	NM_001354475.2		c.-392+32134T>A		intron	N/A	NP_001341404.1	Q8TDX6-1
	CSGALNACT1	NM_001354476.2		c.-392+75099T>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+74435T>A		intron	N/A	ENSP00000509853.1	Q8TDX6-1
	CSGALNACT1	ENST00000950543.1		c.-602T>A		5_prime_UTR	Exon 1 of 10	ENSP00000620602.1
	CSGALNACT1	ENST00000950544.1		c.-566T>A		5_prime_UTR	Exon 1 of 10	ENSP00000620603.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000768 AC: 1 AN: 130262 AF XY: 0.0000141

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000331 AC: 1 AN: 301762 Hom.: 0 Cov.: 0 AF XY: 0.00000581 AC XY: 1 AN XY: 171980

African (AFR) AF: 0.00 AC: 0 AN: 8554

American (AMR) AF: 0.00 AC: 0 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10784

East Asian (EAS) AF: 0.00 AC: 0 AN: 9210

South Asian (SAS) AF: 0.0000168 AC: 1 AN: 59646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1150

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 158734

Other (OTH) AF: 0.00 AC: 0 AN: 14040

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.13
DANN	Benign	0.50
PhyloP100		-1.5
PromoterAI		-0.051	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11204064; hg19: chr8-19540262;