8-19682751-A-G

Variant names:

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

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+74435T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 453,790 control chromosomes in the GnomAD database, including 51,880 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 0.47 (17040 hom., cov: 32)
  • Exomes 𝑓: 0.48 (34840 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

ENSG00000253270 (HGNC:58187):

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 (SAS) allele frequency at 95% confidence interval = 0.522 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSGALNACT1	NM_001354483.2	MANE Select	c.-392+74435T>C		intron	N/A	NP_001341412.1
	CSGALNACT1	NR_024040.3		n.11T>C		non_coding_transcript_exon	Exon 1 of 10
	CSGALNACT1	NM_001354475.2		c.-392+32134T>C		intron	N/A	NP_001341404.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSGALNACT1	ENST00000692225.2	MANE Select	c.-392+74435T>C		intron	N/A	ENSP00000509853.1
	CSGALNACT1	ENST00000397998.7	TSL:2	n.-447T>C		non_coding_transcript_exon	Exon 1 of 10	ENSP00000381084.3
	CSGALNACT1	ENST00000397998.7	TSL:2	n.-447T>C		5_prime_UTR	Exon 1 of 10	ENSP00000381084.3

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71648 AN: 151942 Hom.: 17023 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.465

GnomAD2 exomes AF: 0.467 AC: 60775 AN: 130262 AF XY: 0.473

Gnomad AFR exome AF: 0.505

Gnomad AMR exome AF: 0.422

Gnomad ASJ exome AF: 0.406

Gnomad EAS exome AF: 0.459

Gnomad FIN exome AF: 0.421

Gnomad NFE exome AF: 0.469

Gnomad OTH exome AF: 0.474

GnomAD4 exome AF: 0.477 AC: 144011 AN: 301734 Hom.: 34840 Cov.: 0 AF XY: 0.484 AC XY: 83207 AN XY: 171966

African (AFR) AF: 0.500 AC: 4279 AN: 8554

American (AMR) AF: 0.422 AC: 11502 AN: 27270

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 4410 AN: 10784

East Asian (EAS) AF: 0.463 AC: 4262 AN: 9208

South Asian (SAS) AF: 0.532 AC: 31738 AN: 59642

European-Finnish (FIN) AF: 0.431 AC: 5332 AN: 12370

Middle Eastern (MID) AF: 0.467 AC: 536 AN: 1148

European-Non Finnish (NFE) AF: 0.475 AC: 75332 AN: 158720

Other (OTH) AF: 0.472 AC: 6620 AN: 14038

GnomAD4 genome AF: 0.472 AC: 71698 AN: 152056 Hom.: 17040 Cov.: 32 AF XY: 0.468 AC XY: 34765 AN XY: 74302

African (AFR) AF: 0.495 AC: 20532 AN: 41490

American (AMR) AF: 0.449 AC: 6862 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1359 AN: 3470

East Asian (EAS) AF: 0.443 AC: 2287 AN: 5162

South Asian (SAS) AF: 0.539 AC: 2596 AN: 4814

European-Finnish (FIN) AF: 0.410 AC: 4328 AN: 10556

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 31990 AN: 67944

Other (OTH) AF: 0.473 AC: 1001 AN: 2116

Alfa AF: 0.471 Hom.: 23346

Bravo AF: 0.474

Asia WGS AF: 0.498 AC: 1728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.44
PhyloP100		-1.5
PromoterAI		0.21	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: rs11204064; hg19: chr8-19540262;