22-42058489-GA-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000262.3(NAGA):​c.*1789del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.89 ( 60221 hom., cov: 0)
Failed GnomAD Quality Control

Consequence

NAGA
NM_000262.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 1.27
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]
WBP2NL (HGNC:28389): (WBP2 N-terminal like) WBP2NL is a sperm-specific WW domain-binding protein that promotes meiotic resumption and pronuclear development during oocyte fertilization (Wu et al., 2007 [PubMed 17289678]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NAGANM_000262.3 linkuse as main transcriptc.*1789del 3_prime_UTR_variant 9/9 ENST00000396398.8 NP_000253.1
NAGANM_001362848.1 linkuse as main transcriptc.*1789del 3_prime_UTR_variant 10/10 NP_001349777.1
NAGANM_001362850.1 linkuse as main transcriptc.*1789del 3_prime_UTR_variant 10/10 NP_001349779.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NAGAENST00000396398.8 linkuse as main transcriptc.*1789del 3_prime_UTR_variant 9/91 NM_000262.3 ENSP00000379680 P1
WBP2NLENST00000436265.5 linkuse as main transcript downstream_gene_variant 2 ENSP00000401002

Frequencies

GnomAD3 genomes
AF:
0.887
AC:
134083
AN:
151110
Hom.:
60206
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.734
Gnomad AMI
AF:
0.996
Gnomad AMR
AF:
0.954
Gnomad ASJ
AF:
0.950
Gnomad EAS
AF:
0.998
Gnomad SAS
AF:
0.990
Gnomad FIN
AF:
0.930
Gnomad MID
AF:
0.911
Gnomad NFE
AF:
0.937
Gnomad OTH
AF:
0.915
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AC:
0
AN:
0
Hom.:
0
Cov.:
0
AC XY:
0
AN XY:
0
GnomAD4 genome
AF:
0.887
AC:
134144
AN:
151224
Hom.:
60221
Cov.:
0
AF XY:
0.890
AC XY:
65761
AN XY:
73858
show subpopulations
Gnomad4 AFR
AF:
0.734
Gnomad4 AMR
AF:
0.954
Gnomad4 ASJ
AF:
0.950
Gnomad4 EAS
AF:
0.998
Gnomad4 SAS
AF:
0.990
Gnomad4 FIN
AF:
0.930
Gnomad4 NFE
AF:
0.937
Gnomad4 OTH
AF:
0.916

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Alpha-N-acetylgalactosaminidase deficiency type 2 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Alpha-N-acetylgalactosaminidase deficiency type 1 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10713176; hg19: chr22-42454493; API