rs133376

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000898674.1(NAGA):c.-70+183G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 166,156 control chromosomes in the GnomAD database, including 13,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 11709 hom., cov: 34)

Exomes 𝑓: 0.49 ( 1755 hom. )

Consequence

NAGA
ENST00000898674.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.190

Publications

20 publications found

Variant links:

Genes affected

NAGA (HGNC:7631): (alpha-N-acetylgalactosaminidase) NAGA encodes the lysosomal enzyme alpha-N-acetylgalactosaminidase, which cleaves alpha-N-acetylgalactosaminyl moieties from glycoconjugates. Mutations in NAGA have been identified as the cause of Schindler disease types I and II (type II also known as Kanzaki disease). [provided by RefSeq, Jul 2008]

NAGA Gene-Disease associations (from GenCC):

alpha-N-acetylgalactosaminidase deficiency
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
alpha-N-acetylgalactosaminidase deficiency type 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Orphanet
alpha-N-acetylgalactosaminidase deficiency type 1
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
alpha-N-acetylgalactosaminidase deficiency type 3
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

NAGA links:

ENSG00000286659 (HGNC:):

ENSG00000286659 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000898674.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 22-42070901-C-T is Benign according to our data. Variant chr22-42070901-C-T is described in ClinVar as Benign. ClinVar VariationId is 684292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000898674.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NAGA	NM_000262.3	MANE Select	c.-604G>A	upstream_gene	N/A	NP_000253.1	P17050
NAGA	NM_001362848.1		c.-215G>A	upstream_gene	N/A	NP_001349777.1	P17050
NAGA	NM_001362850.1		c.-208G>A	upstream_gene	N/A	NP_001349779.1	P17050

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NAGA	ENST00000898674.1		c.-70+183G>A	intron	N/A	ENSP00000568733.1
NAGA	ENST00000958241.1		c.-77+183G>A	intron	N/A	ENSP00000628300.1
NAGA	ENST00000396398.8	TSL:1 MANE Select	c.-604G>A	upstream_gene	N/A	ENSP00000379680.3	P17050

Frequencies

GnomAD3 genomes

AF:

0.359

AC:

54592

AN:

152072

Hom.:

11697

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.489

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.361

Gnomad EAS

AF:

0.324

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.503

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.448

Gnomad OTH

AF:

0.383

GnomAD4 exome

AF:

0.491

AC:

6860

AN:

13966

Hom.:

1755

AF XY:

0.492

AC XY:

3740

AN XY:

7602

show subpopulations

African (AFR)

AF:

0.169

AC:

AN:

242

American (AMR)

AF:

0.541

AC:

1363

AN:

2518

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

AN:

100

East Asian (EAS)

AF:

0.381

AC:

282

AN:

740

South Asian (SAS)

AF:

0.498

AC:

1315

AN:

2640

European-Finnish (FIN)

AF:

0.590

AC:

131

AN:

222

Middle Eastern (MID)

AF:

0.536

AC:

AN:

European-Non Finnish (NFE)

AF:

0.492

AC:

3404

AN:

6918

Other (OTH)

AF:

0.486

AC:

271

AN:

558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

165

329

494

658

823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<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:

0.359

AC:

54610

AN:

152190

Hom.:

11709

Cov.:

AF XY:

0.365

AC XY:

27183

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.116

AC:

4838

AN:

41544

American (AMR)

AF:

0.489

AC:

7479

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.361

AC:

1255

AN:

3472

East Asian (EAS)

AF:

0.325

AC:

1677

AN:

5160

South Asian (SAS)

AF:

0.453

AC:

2184

AN:

4824

European-Finnish (FIN)

AF:

0.503

AC:

5324

AN:

10586

Middle Eastern (MID)

AF:

0.342

AC:

100

AN:

292

European-Non Finnish (NFE)

AF:

0.448

AC:

30483

AN:

67984

Other (OTH)

AF:

0.389

AC:

824

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1664

3329

4993

6658

8322

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

518

1036

1554

2072

2590

<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:

0.395

Hom.:

3161

Bravo

AF:

0.350

Asia WGS

AF:

0.414

AC:

1438

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

-0.19

PromoterAI

-0.25

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over