dbSNP rs2435381: CSGALNACT2:p.Pro479Ser (chr10-43183348-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_018590.5(CSGALNACT2):c.1435C>T(p.Pro479Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,613,590 control chromosomes in the GnomAD database, including 54,615 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 3953 hom., cov: 32)

Exomes 𝑓: 0.26 ( 50662 hom. )

Consequence

CSGALNACT2
NM_018590.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.96

Publications

20 publications found

Variant links:

Genes affected

CSGALNACT2 (HGNC:24292): (chondroitin sulfate N-acetylgalactosaminyltransferase 2) This gene encodes a member of the chondroitin N-acetylgalactosaminyltransferase family. The encoded protein is involved in elongation during chondroitin sulfate synthesis. Alternative splicing of this gene results in multiple transcript variants. Two related pseudogenes have been identified on chromosome X. [provided by RefSeq, Feb 2016]

CSGALNACT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0014256835).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSGALNACT2	NM_018590.5 link	c.1435C>T	p.Pro479Ser	missense_variant	Exon 8 of 8	ENST00000374466.4	NP_061060.3	Q8N6G5-1A0A0S2Z5F5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSGALNACT2	ENST00000374466.4 link	c.1435C>T	p.Pro479Ser	missense_variant	Exon 8 of 8	1	NM_018590.5	ENSP00000363590.3		Q8N6G5-1

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31637

AN:

151930

Hom.:

3943

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0666

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.229

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.207

GnomAD2 exomes

AF:

0.232

AC:

58350

AN:

251466

AF XY:

0.235

show subpopulations

Gnomad AFR exome

AF:

0.0632

Gnomad AMR exome

AF:

0.169

Gnomad ASJ exome

AF:

0.229

Gnomad EAS exome

AF:

0.232

Gnomad FIN exome

AF:

0.319

Gnomad NFE exome

AF:

0.275

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.258

AC:

377267

AN:

1461542

Hom.:

50662

Cov.:

AF XY:

0.256

AC XY:

186359

AN XY:

727090

show subpopulations

African (AFR)

AF:

0.0547

AC:

1832

AN:

33472

American (AMR)

AF:

0.173

AC:

7750

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

5912

AN:

26134

East Asian (EAS)

AF:

0.215

AC:

8528

AN:

39698

South Asian (SAS)

AF:

0.173

AC:

14954

AN:

86248

European-Finnish (FIN)

AF:

0.308

AC:

16457

AN:

53418

Middle Eastern (MID)

AF:

0.208

AC:

1202

AN:

5766

European-Non Finnish (NFE)

AF:

0.275

AC:

305994

AN:

1111710

Other (OTH)

AF:

0.242

AC:

14638

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

15668

31337

47005

62674

78342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9980

19960

29940

39920

49900

<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:

0.208

AC:

31662

AN:

152048

Hom.:

3953

Cov.:

AF XY:

0.212

AC XY:

15740

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.0665

AC:

2761

AN:

41500

American (AMR)

AF:

0.211

AC:

3225

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

798

AN:

3470

East Asian (EAS)

AF:

0.229

AC:

1181

AN:

5162

South Asian (SAS)

AF:

0.167

AC:

806

AN:

4814

European-Finnish (FIN)

AF:

0.324

AC:

3415

AN:

10536

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.274

AC:

18655

AN:

67974

Other (OTH)

AF:

0.213

AC:

450

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1237

2473

3710

4946

6183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

344

688

1032

1376

1720

<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:

0.230

Hom.:

2179

Bravo

AF:

0.193

TwinsUK

AF:

0.270

AC:

1001

ALSPAC

AF:

0.272

AC:

1047

ESP6500AA

AF:

0.0695

AC:

306

ESP6500EA

AF:

0.267

AC:

2293

ExAC

AF:

0.232

AC:

28127

Asia WGS

AF:

0.189

AC:

656

AN:

3478

EpiCase

AF:

0.275

EpiControl

AF:

0.273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.098

Eigen

Benign

0.091

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.91

PhyloP100

3.0

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.12

Sift

Benign

0.19

Sift4G

Benign

0.20

Polyphen

0.13

Vest4

0.034

MPC

0.23

ClinPred

0.026

GERP RS

5.9

Varity_R

0.12

gMVP

0.61

Mutation Taster

=53/47

polymorphism (auto)

(source)

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

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