chr22-42058489-GA-G

Position:

• chr22-42058489-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
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• 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 -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
NAGA	NM_000262.3	c.*1789del		3_prime_UTR_variant	9/9	ENST00000396398.8	NP_000253.1
NAGA	NM_001362848.1	c.*1789del		3_prime_UTR_variant	10/10		NP_001349777.1
NAGA	NM_001362850.1	c.*1789del		3_prime_UTR_variant	10/10		NP_001349779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAGA	ENST00000396398.8	c.*1789del		3_prime_UTR_variant	9/9	1	NM_000262.3	ENSP00000379680	P1
WBP2NL	ENST00000436265.5			downstream_gene_variant		2		ENSP00000401002

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134083 AN: 151110 Hom.: 60206 Cov.: 0

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

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

Submissions by phenotype

Alpha-N-acetylgalactosaminidase deficiency type 2 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Alpha-N-acetylgalactosaminidase deficiency type 1 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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;