rs121434533

Variant names:

• chr22-42061039-C-G
• NM_000262.3:c.986G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-42061039-C-G
• chr22-42061039-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_000262.3(NAGA):​c.986G>C​(p.Arg329Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.10

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.945

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAGA	NM_000262.3	c.986G>C	p.Arg329Pro	missense_variant	Exon 8 of 9	ENST00000396398.8	NP_000253.1
NAGA	NM_001362848.1	c.986G>C	p.Arg329Pro	missense_variant	Exon 9 of 10		NP_001349777.1
NAGA	NM_001362850.1	c.986G>C	p.Arg329Pro	missense_variant	Exon 9 of 10		NP_001349779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAGA	ENST00000396398.8	c.986G>C	p.Arg329Pro	missense_variant	Exon 8 of 9	1	NM_000262.3	ENSP00000379680.3
NAGA	ENST00000402937.1	c.986G>C	p.Arg329Pro	missense_variant	Exon 9 of 10	5		ENSP00000384603.1
NAGA	ENST00000403363.5	c.986G>C	p.Arg329Pro	missense_variant	Exon 9 of 10	5		ENSP00000385283.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.96	D;D;D
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	.;.;D
M_CAP	Pathogenic	0.35	D
MetaRNN	Pathogenic	0.94	D;D;D
MetaSVM	Pathogenic	0.98	D
MutationAssessor	Pathogenic	4.2	H;H;H
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-5.7	D;D;D
REVEL	Pathogenic	0.83
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.88
MutPred		0.68		Loss of MoRF binding (P = 0.0191);Loss of MoRF binding (P = 0.0191);Loss of MoRF binding (P = 0.0191);
MVP		0.97
MPC		0.94
ClinPred		1.0	D
GERP RS		4.7
Varity_R		1.0
gMVP		0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-42457043;