22-42058489-GAA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000262.3(NAGA):c.*1788_*1789del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.072 (1349 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: NAGA NM_000262.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.27

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 22-42058489-GAA-G is Benign according to our data. Variant chr22-42058489-GAA-G is described in ClinVar as [Benign]. Clinvar id is 341888.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAGA	NM_000262.3	c.*1788_*1789del		3_prime_UTR_variant	9/9	ENST00000396398.8
NAGA	NM_001362848.1	c.*1788_*1789del		3_prime_UTR_variant	10/10
NAGA	NM_001362850.1	c.*1788_*1789del		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAGA	ENST00000396398.8	c.*1788_*1789del		3_prime_UTR_variant	9/9	1	NM_000262.3	P1
WBP2NL	ENST00000436265.5			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0721 AC: 10903 AN: 151130 Hom.: 1338 Cov.: 0

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00167

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.00133

Gnomad OTH AF: 0.0431

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0724 AC: 10945 AN: 151244 Hom.: 1349 Cov.: 0 AF XY: 0.0695 AC XY: 5133 AN XY: 73858

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.0222

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00167

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00133

Gnomad4 OTH AF: 0.0427

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Alpha-N-acetylgalactosaminidase deficiency type 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Alpha-N-acetylgalactosaminidase deficiency type 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs10713176; hg19: chr22-42454493;