22-42058946-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000262.3(NAGA):​c.*1333T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 152,178 control chromosomes in the GnomAD database, including 14,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 14435 hom., cov: 32)
Exomes 𝑓: 0.50 ( 1 hom. )

Consequence

NAGA
NM_000262.3 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0280
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 22-42058946-A-G is Benign according to our data. Variant chr22-42058946-A-G is described in ClinVar as [Benign]. Clinvar id is 341891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NAGANM_000262.3 linkuse as main transcriptc.*1333T>C 3_prime_UTR_variant 9/9 ENST00000396398.8 NP_000253.1
NAGANM_001362848.1 linkuse as main transcriptc.*1333T>C 3_prime_UTR_variant 10/10 NP_001349777.1
NAGANM_001362850.1 linkuse as main transcriptc.*1333T>C 3_prime_UTR_variant 10/10 NP_001349779.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NAGAENST00000396398.8 linkuse as main transcriptc.*1333T>C 3_prime_UTR_variant 9/91 NM_000262.3 ENSP00000379680 P1

Frequencies

GnomAD3 genomes
AF:
0.396
AC:
60161
AN:
152040
Hom.:
14425
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.132
Gnomad AMI
AF:
0.545
Gnomad AMR
AF:
0.509
Gnomad ASJ
AF:
0.416
Gnomad EAS
AF:
0.848
Gnomad SAS
AF:
0.507
Gnomad FIN
AF:
0.514
Gnomad MID
AF:
0.373
Gnomad NFE
AF:
0.467
Gnomad OTH
AF:
0.416
GnomAD4 exome
AF:
0.500
AC:
10
AN:
20
Hom.:
1
Cov.:
0
AF XY:
0.444
AC XY:
8
AN XY:
18
show subpopulations
Gnomad4 NFE exome
AF:
0.500
GnomAD4 genome
AF:
0.395
AC:
60178
AN:
152158
Hom.:
14435
Cov.:
32
AF XY:
0.404
AC XY:
30077
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.131
Gnomad4 AMR
AF:
0.509
Gnomad4 ASJ
AF:
0.416
Gnomad4 EAS
AF:
0.849
Gnomad4 SAS
AF:
0.507
Gnomad4 FIN
AF:
0.514
Gnomad4 NFE
AF:
0.467
Gnomad4 OTH
AF:
0.422
Alfa
AF:
0.456
Hom.:
16806
Bravo
AF:
0.389
Asia WGS
AF:
0.635
AC:
2206
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Alpha-N-acetylgalactosaminidase deficiency type 2 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Alpha-N-acetylgalactosaminidase deficiency type 1 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
1.2
DANN
Benign
0.66
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1063392; hg19: chr22-42454950; API