Variant rs144771084 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000262.3(NAGA):c.1142G>C(p.Arg381Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

NAGA
NM_000262.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.73

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15912345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NAGA	NM_000262.3 linkuse as main transcript	c.1142G>C	p.Arg381Pro	missense_variant	9/9	ENST00000396398.8	NP_000253.1
NAGA	NM_001362848.1 linkuse as main transcript	c.1142G>C	p.Arg381Pro	missense_variant	10/10		NP_001349777.1
NAGA	NM_001362850.1 linkuse as main transcript	c.1142G>C	p.Arg381Pro	missense_variant	10/10		NP_001349779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
NAGA	ENST00000396398.8 linkuse as main transcript	c.1142G>C	p.Arg381Pro	missense_variant	9/9	1	NM_000262.3	ENSP00000379680	P1
NAGA	ENST00000402937.1 linkuse as main transcript	c.1142G>C	p.Arg381Pro	missense_variant	10/10	5		ENSP00000384603	P1
NAGA	ENST00000403363.5 linkuse as main transcript	c.1142G>C	p.Arg381Pro	missense_variant	10/10	5		ENSP00000385283	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

0.14

DANN

Benign

0.76

DEOGEN2

Uncertain

0.63

D;D;D

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.68

.;.;T

M_CAP

Benign

0.064

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.0

M;M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.24

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.24

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.20

MutPred

0.49

Gain of glycosylation at S378 (P = 0.036);Gain of glycosylation at S378 (P = 0.036);Gain of glycosylation at S378 (P = 0.036);

MVP

0.49

MPC

0.30

ClinPred

0.12

GERP RS

-9.2

Varity_R

0.24

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over