22-42058489-GAA-GAAA

Variant names:

• chr22-42058489-G-GA
• rs10713176
• NM_000262.3:c.*1789dupT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_000262.3(NAGA):​c.*1789dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00040 (0 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: NAGA NM_000262.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000397 (60/151272) while in subpopulation AFR AF= 0.00124 (51/41270). AF 95% confidence interval is 0.000965. There are 0 homozygotes in gnomad4. There are 34 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAGA	NM_000262.3	c.*1789dupT		3_prime_UTR_variant	Exon 9 of 9	ENST00000396398.8	NP_000253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAGA	ENST00000396398	c.*1789dupT		3_prime_UTR_variant	Exon 9 of 9	1	NM_000262.3	ENSP00000379680.3
WBP2NL	ENST00000436265.5	n.*473_*474insA		downstream_gene_variant		2		ENSP00000401002.1

Frequencies

GnomAD3 genomes AF: 0.000397 AC: 60 AN: 151158 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000331

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.000484

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: 0.000397 AC: 60 AN: 151272 Hom.: 0 Cov.: 0 AF XY: 0.000460 AC XY: 34 AN XY: 73878

Gnomad4 AFR AF: 0.00124

Gnomad4 AMR AF: 0.000330

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000442

Gnomad4 OTH AF: 0.000479

ClinVar

Not reported in ClinVar

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;