rs11703233

Variant names:

• chr22-42058583-G-A
• rs11703233
• NM_000262.3:c.*1696C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000262.3(NAGA):​c.*1696C>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 0.0112 in 152,258 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (22 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NAGA NM_000262.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.45
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 22-42058583-G-A is Benign according to our data. Variant chr22-42058583-G-A is described in ClinVar as Benign. ClinVar VariationId is 341889.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0112 (1699/152258) while in subpopulation SAS AF = 0.0313 (151/4820). AF 95% confidence interval is 0.0273. There are 22 homozygotes in GnomAd4. There are 851 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

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.*1696C>T		3_prime_UTR	Exon 9 of 9	NP_000253.1	P17050
	NAGA	NM_001362848.1		c.*1696C>T		3_prime_UTR	Exon 10 of 10	NP_001349777.1	P17050
	NAGA	NM_001362850.1		c.*1696C>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.*1696C>T		3_prime_UTR	Exon 9 of 9	ENSP00000379680.3	P17050
	NAGA	ENST00000898671.1		c.*1696C>T		3_prime_UTR	Exon 9 of 9	ENSP00000568730.1
	NAGA	ENST00000898673.1		c.*1696C>T		3_prime_UTR	Exon 9 of 9	ENSP00000568732.1

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1700 AN: 152140 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.00200

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.00923

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.0186

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0126

Gnomad OTH AF: 0.0115

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

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: 0.00 AC: 0 AN: 10

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0112 AC: 1699 AN: 152258 Hom.: 22 Cov.: 32 AF XY: 0.0114 AC XY: 851 AN XY: 74450

African (AFR) AF: 0.00200 AC: 83 AN: 41528

American (AMR) AF: 0.00922 AC: 141 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0507 AC: 176 AN: 3470

East Asian (EAS) AF: 0.0185 AC: 96 AN: 5190

South Asian (SAS) AF: 0.0313 AC: 151 AN: 4820

European-Finnish (FIN) AF: 0.0116 AC: 123 AN: 10610

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0126 AC: 858 AN: 68022

Other (OTH) AF: 0.0114 AC: 24 AN: 2112

Alfa AF: 0.0122 Hom.: 25

Bravo AF: 0.0107

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Alpha-N-acetylgalactosaminidase deficiency type 1 (1)
-	-	1	Alpha-N-acetylgalactosaminidase deficiency type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.95
DANN	Benign	0.57
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs11703233; hg19: chr22-42454587;