rs752527478

Positions:

• chr17-42544122-C-G
• chr17-42544122-C-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.2116C>G​(p.Gln706Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 6.8e-7 (0 hom.)
• Consequence: NAGLU NM_000263.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.714

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]

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=0.16355437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAGLU	NM_000263.4	c.2116C>G	p.Gln706Glu	missense_variant	6/6	ENST00000225927.7	NP_000254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAGLU	ENST00000225927.7	c.2116C>G	p.Gln706Glu	missense_variant	6/6	1	NM_000263.4	ENSP00000225927	P1
NAGLU	ENST00000591587.1	c.*1085C>G		3_prime_UTR_variant	4/4	5		ENSP00000467836

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251326 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135862

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461840 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727214

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	15
DANN	Benign	0.67
DEOGEN2	Uncertain	0.57	D
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.16	T
MetaSVM	Uncertain	-0.051	T
MutationAssessor	Benign	0.81	L
MutationTaster	Benign	0.88	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.030	N
REVEL	Uncertain	0.32
Sift	Benign	0.90	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.10
MutPred		0.55		Gain of solvent accessibility (P = 0.0411);
MVP		0.86
MPC		0.39
ClinPred		0.037	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.23

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: rs752527478; hg19: chr17-40696140;