Genetic Variant CSGALNACT1:c.-392+74575G>A (chr8-19682611-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001354483.2(CSGALNACT1):c.-392+74575G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 453,750 control chromosomes in the GnomAD database, including 10,794 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 0.22 ( 3967 hom., cov: 31)

Exomes 𝑓: 0.20 ( 6827 hom. )

Consequence

CSGALNACT1
NM_001354483.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

Publications

7 publications found

Variant links:

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

CSGALNACT1 links:

ENSG00000253270 (HGNC:58187):

ENSG00000253270 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSGALNACT1	NM_001354483.2 link	c.-392+74575G>A		intron_variant	Intron 1 of 8	ENST00000692225.2	NP_001341412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSGALNACT1	ENST00000692225.2 link	c.-392+74575G>A		intron_variant	Intron 1 of 8		NM_001354483.2	ENSP00000509853.1		Q8TDX6-1

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33316

AN:

151906

Hom.:

3944

Cov.:

show subpopulations

Gnomad AFR

AF:

0.290

Gnomad AMI

AF:

0.194

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.409

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.198

GnomAD4 exome

AF:

0.203

AC:

61382

AN:

301730

Hom.:

6827

Cov.:

AF XY:

0.205

AC XY:

35228

AN XY:

171974

show subpopulations

African (AFR)

AF:

0.288

AC:

2463

AN:

8554

American (AMR)

AF:

0.247

AC:

6730

AN:

27268

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

1442

AN:

10780

East Asian (EAS)

AF:

0.429

AC:

3948

AN:

9208

South Asian (SAS)

AF:

0.230

AC:

13693

AN:

59648

European-Finnish (FIN)

AF:

0.162

AC:

2002

AN:

12364

Middle Eastern (MID)

AF:

0.150

AC:

172

AN:

1150

European-Non Finnish (NFE)

AF:

0.177

AC:

28145

AN:

158718

Other (OTH)

AF:

0.199

AC:

2787

AN:

14040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2923

5846

8768

11691

14614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

278

556

834

1112

1390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.220

AC:

33372

AN:

152020

Hom.:

3967

Cov.:

AF XY:

0.219

AC XY:

16271

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.291

AC:

12038

AN:

41434

American (AMR)

AF:

0.220

AC:

3365

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

440

AN:

3472

East Asian (EAS)

AF:

0.409

AC:

2104

AN:

5148

South Asian (SAS)

AF:

0.243

AC:

1173

AN:

4818

European-Finnish (FIN)

AF:

0.151

AC:

1593

AN:

10578

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.177

AC:

12000

AN:

67962

Other (OTH)

AF:

0.208

AC:

439

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1321

2642

3964

5285

6606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.194

Hom.:

12951

Bravo

AF:

0.229

Asia WGS

AF:

0.328

AC:

1139

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.13

(source)

DANN

Benign

0.34

PhyloP100

-1.1

PromoterAI

-0.051

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over