NM_001354483.2:c.1449C>T

Variant names:

• chr8-19405930-G-A
• rs35971700
• NM_001354483.2:c.1449C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001354483.2(CSGALNACT1):​c.1449C>T​(p.Asp483Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0657 in 1,614,034 control chromosomes in the GnomAD database, including 3,765 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (269 hom., cov: 31)
  • Exomes 𝑓: 0.067 (3496 hom.)
• Consequence: CSGALNACT1 NM_001354483.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.71
• Publications: 12 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 8-19405930-G-A is Benign according to our data. Variant chr8-19405930-G-A is described in ClinVar as Benign. ClinVar VariationId is 1275470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.71 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0703 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.1449C>T	p.Asp483Asp	synonymous	Exon 9 of 9	NP_001341412.1	Q8TDX6-1
	CSGALNACT1	NM_001130518.2		c.1449C>T	p.Asp483Asp	synonymous	Exon 10 of 10	NP_001123990.1	Q8TDX6-1
	CSGALNACT1	NM_001354475.2		c.1449C>T	p.Asp483Asp	synonymous	Exon 10 of 10	NP_001341404.1	Q8TDX6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSGALNACT1	ENST00000692225.2	MANE Select	c.1449C>T	p.Asp483Asp	synonymous	Exon 9 of 9	ENSP00000509853.1	Q8TDX6-1
	CSGALNACT1	ENST00000332246.10	TSL:1	c.1449C>T	p.Asp483Asp	synonymous	Exon 10 of 10	ENSP00000330805.6	Q8TDX6-1
	CSGALNACT1	ENST00000454498.6	TSL:1	c.1449C>T	p.Asp483Asp	synonymous	Exon 10 of 10	ENSP00000411816.2	Q8TDX6-1

Frequencies

GnomAD3 genomes AF: 0.0556 AC: 8451 AN: 152040 Hom.: 271 Cov.: 31

Gnomad AFR AF: 0.0287

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0508

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0145

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.0523

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0720

Gnomad OTH AF: 0.0664

GnomAD2 exomes AF: 0.0616 AC: 15497 AN: 251432 AF XY: 0.0639

Gnomad AFR exome AF: 0.0263

Gnomad AMR exome AF: 0.0392

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.0166

Gnomad FIN exome AF: 0.0593

Gnomad NFE exome AF: 0.0722

Gnomad OTH exome AF: 0.0724

GnomAD4 exome AF: 0.0668 AC: 97644 AN: 1461876 Hom.: 3496 Cov.: 32 AF XY: 0.0673 AC XY: 48976 AN XY: 727238

African (AFR) AF: 0.0278 AC: 932 AN: 33480

American (AMR) AF: 0.0409 AC: 1828 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2967 AN: 26136

East Asian (EAS) AF: 0.0163 AC: 649 AN: 39700

South Asian (SAS) AF: 0.0729 AC: 6290 AN: 86258

European-Finnish (FIN) AF: 0.0631 AC: 3373 AN: 53420

Middle Eastern (MID) AF: 0.108 AC: 625 AN: 5768

European-Non Finnish (NFE) AF: 0.0691 AC: 76810 AN: 1111994

Other (OTH) AF: 0.0690 AC: 4170 AN: 60396

GnomAD4 genome AF: 0.0555 AC: 8452 AN: 152158 Hom.: 269 Cov.: 31 AF XY: 0.0546 AC XY: 4061 AN XY: 74370

African (AFR) AF: 0.0286 AC: 1189 AN: 41512

American (AMR) AF: 0.0508 AC: 776 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 390 AN: 3468

East Asian (EAS) AF: 0.0145 AC: 75 AN: 5160

South Asian (SAS) AF: 0.0692 AC: 332 AN: 4800

European-Finnish (FIN) AF: 0.0523 AC: 554 AN: 10602

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0720 AC: 4896 AN: 68012

Other (OTH) AF: 0.0657 AC: 139 AN: 2116

Alfa AF: 0.0642 Hom.: 573

Bravo AF: 0.0543

Asia WGS AF: 0.0510 AC: 179 AN: 3478

EpiCase AF: 0.0753

EpiControl AF: 0.0768

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.24
DANN	Benign	0.50
PhyloP100		-2.7
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: rs35971700; hg19: chr8-19263441; COSMIC: COSV59974823;