rs1445294968

Variant names:

• chr17-42536630-G-A
• rs1445294968
• NM_000263.4:c.358G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-42536630-G-A
• chr17-42536630-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000263.4(NAGLU):​c.358G>A​(p.Glu120Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000371 in 1,347,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 33)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: NAGLU NM_000263.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.568

Genes affected

NAGLU (HGNC:7632): (N-acetyl-alpha-glucosaminidase) This gene encodes an enzyme that degrades heparan sulfate by hydrolysis of terminal N-acetyl-D-glucosamine residues in N-acetyl-alpha-D-glucosaminides. Defects in this gene are the cause of mucopolysaccharidosis type IIIB (MPS-IIIB), also known as Sanfilippo syndrome B. This disease is characterized by the lysosomal accumulation and urinary excretion of heparan sulfate. [provided by RefSeq, Jul 2008]

ENSG00000266929 (HGNC:):

ACMG classification

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=0.21242508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAGLU	NM_000263.4	c.358G>A	p.Glu120Lys	missense_variant	Exon 1 of 6	ENST00000225927.7	NP_000254.2
NAGLU	XM_024450771.2	c.358G>A	p.Glu120Lys	missense_variant	Exon 1 of 7		XP_024306539.1
NAGLU	XM_047436138.1	c.-104G>A		5_prime_UTR_variant	Exon 1 of 5		XP_047292094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAGLU	ENST00000225927.7	c.358G>A	p.Glu120Lys	missense_variant	Exon 1 of 6	1	NM_000263.4	ENSP00000225927.1
NAGLU	ENST00000586516.5	c.107G>A	p.Gly36Glu	missense_variant	Exon 1 of 4	2		ENSP00000467135.1
NAGLU	ENST00000591587.1	c.101G>A	p.Gly34Glu	missense_variant	Exon 1 of 4	5		ENSP00000467836.1
ENSG00000266929	ENST00000585572.1	n.121G>A		non_coding_transcript_exon_variant	Exon 1 of 5	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000371 AC: 5 AN: 1347404 Hom.: 0 Cov.: 30 AF XY: 0.00000301 AC XY: 2 AN XY: 664274

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000397

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000188

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	17
DANN	Benign	0.81
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.91	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	0.13	D
MutationAssessor	Benign	-0.43	N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.66	N
REVEL	Uncertain	0.34
Sift	Benign	0.94	T
Sift4G	Benign	0.94	T
Polyphen		0.017	B
Vest4		0.083
MutPred		0.51		Gain of ubiquitination at E120 (P = 0.0267);
MVP		0.72
MPC		0.42
ClinPred		0.11	T
GERP RS		1.4
Varity_R		0.21
gMVP		0.61

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

Other links and lift over

dbSNP: rs1445294968; hg19: chr17-40688648;