12-64713671-T-TAA

Position:

• chr12-64713671-T-TAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002076.4(GNS):​c.*3068_*3069dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0431 in 152,214 control chromosomes in the GnomAD database, including 494 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.043 (494 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GNS NM_002076.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.489

Genes affected

GNS (HGNC:4422): (glucosamine (N-acetyl)-6-sulfatase) The product of this gene is a lysosomal enzyme found in all cells. It is involved in the catabolism of heparin, heparan sulphate, and keratan sulphate. Deficiency of this enzyme results in the accumulation of undegraded substrate and the lysosomal storage disorder mucopolysaccharidosis type IIID (Sanfilippo D syndrome). Mucopolysaccharidosis type IIID is the least common of the four subtypes of Sanfilippo syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-64713671-T-TAA is Benign according to our data. Variant chr12-64713671-T-TAA is described in ClinVar as [Likely_benign]. Clinvar id is 310163.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNS	NM_002076.4	c.*3068_*3069dupTT		3_prime_UTR_variant	14/14	ENST00000258145.8	NP_002067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNS	ENST00000258145	c.*3068_*3069dupTT		3_prime_UTR_variant	14/14	1	NM_002076.4	ENSP00000258145.3
GNS	ENST00000418919	c.*3068_*3069dupTT		3_prime_UTR_variant	13/13	1		ENSP00000413130.2

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6549 AN: 152096 Hom.: 492 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0287

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 298 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 188

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0431 AC: 6566 AN: 152214 Hom.: 494 Cov.: 32 AF XY: 0.0412 AC XY: 3063 AN XY: 74430

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.00614 Hom.: 4

Bravo AF: 0.0486

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Sanfilippo syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs397946778; hg19: chr12-65107451;