chr22-42058350-G-A

Variant names:

• chr22-42058350-G-A
• rs5758566
• NM_000262.3:c.*1929C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000262.3(NAGA):​c.*1929C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,864 control chromosomes in the GnomAD database, including 30,224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (30222 hom., cov: 30)
  • Exomes 𝑓: 1.0 (2 hom.)
• Consequence: NAGA NM_000262.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.585
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 22-42058350-G-A is Benign according to our data. Variant chr22-42058350-G-A is described in ClinVar as Benign. ClinVar VariationId is 341885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000262.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAGA	NM_000262.3	MANE Select	c.*1929C>T		3_prime_UTR	Exon 9 of 9	NP_000253.1	P17050
	NAGA	NM_001362848.1		c.*1929C>T		3_prime_UTR	Exon 10 of 10	NP_001349777.1	P17050
	NAGA	NM_001362850.1		c.*1929C>T		3_prime_UTR	Exon 10 of 10	NP_001349779.1	P17050

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAGA	ENST00000396398.8	TSL:1 MANE Select	c.*1929C>T		3_prime_UTR	Exon 9 of 9	ENSP00000379680.3	P17050
	WBP2NL	ENST00000436265.5	TSL:2	n.*334G>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000401002.1	Q6ICG8
	WBP2NL	ENST00000436265.5	TSL:2	n.*334G>A		3_prime_UTR	Exon 9 of 9	ENSP00000401002.1	Q6ICG8

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94885 AN: 151742 Hom.: 30220 Cov.: 30

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.630

GnomAD4 exome AF: 1.00 AC: 4 AN: 4 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 4 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.625 AC: 94906 AN: 151860 Hom.: 30222 Cov.: 30 AF XY: 0.624 AC XY: 46292 AN XY: 74222

African (AFR) AF: 0.496 AC: 20525 AN: 41378

American (AMR) AF: 0.675 AC: 10302 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2220 AN: 3472

East Asian (EAS) AF: 0.850 AC: 4394 AN: 5170

South Asian (SAS) AF: 0.617 AC: 2970 AN: 4810

European-Finnish (FIN) AF: 0.616 AC: 6482 AN: 10520

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45807 AN: 67930

Other (OTH) AF: 0.632 AC: 1331 AN: 2106

Alfa AF: 0.669 Hom.: 43144

Bravo AF: 0.627

Asia WGS AF: 0.718 AC: 2499 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Alpha-N-acetylgalactosaminidase deficiency type 1 (1)
-	-	1	Alpha-N-acetylgalactosaminidase deficiency type 2 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.86
DANN	Benign	0.57
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs5758566; hg19: chr22-42454354;