Variant 22-42059244-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000262.3(NAGA):c.*1035G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 152,256 control chromosomes in the GnomAD database, including 356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.058 ( 356 hom., cov: 32)

Exomes 𝑓: 0.080 ( 0 hom. )

Consequence

NAGA
NM_000262.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.221

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]

NAGA links:

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=-0.86).

BP6

Variant 22-42059244-C-T is Benign according to our data. Variant chr22-42059244-C-T is described in ClinVar as [Benign]. Clinvar id is 341895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
NAGA	NM_000262.3 linkuse as main transcript	c.*1035G>A	3_prime_UTR_variant	9/9	ENST00000396398.8	NP_000253.1
NAGA	NM_001362848.1 linkuse as main transcript	c.*1035G>A	3_prime_UTR_variant	10/10		NP_001349777.1
NAGA	NM_001362850.1 linkuse as main transcript	c.*1035G>A	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 linkuse as main transcript	c.*1035G>A		3_prime_UTR_variant	9/9	1	NM_000262.3	ENSP00000379680	P1

Frequencies

GnomAD3 genomes

AF:

0.0578

AC:

8791

AN:

152088

Hom.:

356

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0156

Gnomad AMI

AF:

0.0396

Gnomad AMR

AF:

0.0525

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0292

Gnomad FIN

AF:

0.0471

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0902

Gnomad OTH

AF:

0.0584

GnomAD4 exome

AF:

0.0800

AC:

AN:

Hom.:

Cov.:

AF XY:

0.105

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.105

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0578

AC:

8790

AN:

152206

Hom.:

356

Cov.:

AF XY:

0.0556

AC XY:

4135

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0156

Gnomad4 AMR

AF:

0.0525

Gnomad4 ASJ

AF:

0.115

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0293

Gnomad4 FIN

AF:

0.0471

Gnomad4 NFE

AF:

0.0902

Gnomad4 OTH

AF:

0.0578

Alfa

AF:

0.0808

Hom.:

179

Bravo

AF:

0.0570

Asia WGS

AF:

0.0140

AC:

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 submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This 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 submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Alpha-N-acetylgalactosaminidase deficiency type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.7

DANN

Benign

0.86

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over