Variant 17-80217231-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000199.5(SGSH):c.89-39G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0498 in 1,577,028 control chromosomes in the GnomAD database, including 4,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1758 hom., cov: 33)

Exomes 𝑓: 0.044 ( 2579 hom. )

Consequence

SGSH
NM_000199.5 intron

Scores

Splicing: ADA: 0.0002776

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.196

Variant links:

Genes affected

SGSH (HGNC:10818): (N-sulfoglucosamine sulfohydrolase) This gene encodes the enzyme sulfamidase; one of several enzymes involved in the lysosomal degradation of heparan sulfate. Mutations in this gene are associated with the lysosomal storage disease mucopolysaccaridosis IIIA, also known as Sanfilippo syndrome A, which results from impaired degradation of heparan sulfate. Transcripts of varying sizes have been reported but their biological validity has not been determined. [provided by RefSeq, Jun 2017]

SGSH links:

SGSH (HGNC:):

SGSH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 17-80217231-C-T is Benign according to our data. Variant chr17-80217231-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 255520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGSH	NM_000199.5 linkuse as main transcript	c.89-39G>A		intron_variant		ENST00000326317.11	NP_000190.1	P51688

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGSH	ENST00000326317.11 linkuse as main transcript	c.89-39G>A		intron_variant		1	NM_000199.5	ENSP00000314606.6		P51688

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16250

AN:

152132

Hom.:

1755

Cov.:

show subpopulations

Gnomad AFR

AF:

0.280

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0522

Gnomad ASJ

AF:

0.0594

Gnomad EAS

AF:

0.0198

Gnomad SAS

AF:

0.0511

Gnomad FIN

AF:

0.0678

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0347

Gnomad OTH

AF:

0.0888

GnomAD3 exomes

AF:

0.0593

AC:

11534

AN:

194566

Hom.:

725

AF XY:

0.0563

AC XY:

5901

AN XY:

104900

show subpopulations

Gnomad AFR exome

AF:

0.293

Gnomad AMR exome

AF:

0.0358

Gnomad ASJ exome

AF:

0.0618

Gnomad EAS exome

AF:

0.0185

Gnomad SAS exome

AF:

0.0587

Gnomad FIN exome

AF:

0.0634

Gnomad NFE exome

AF:

0.0394

Gnomad OTH exome

AF:

0.0515

GnomAD4 exome

AF:

0.0437

AC:

62226

AN:

1424778

Hom.:

2579

Cov.:

AF XY:

0.0435

AC XY:

30714

AN XY:

706492

show subpopulations

Gnomad4 AFR exome

AF:

0.294

Gnomad4 AMR exome

AF:

0.0381

Gnomad4 ASJ exome

AF:

0.0612

Gnomad4 EAS exome

AF:

0.0224

Gnomad4 SAS exome

AF:

0.0587

Gnomad4 FIN exome

AF:

0.0631

Gnomad4 NFE exome

AF:

0.0338

Gnomad4 OTH exome

AF:

0.0578

GnomAD4 genome

AF:

0.107

AC:

16283

AN:

152250

Hom.:

1758

Cov.:

AF XY:

0.106

AC XY:

7915

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.280

Gnomad4 AMR

AF:

0.0521

Gnomad4 ASJ

AF:

0.0594

Gnomad4 EAS

AF:

0.0199

Gnomad4 SAS

AF:

0.0509

Gnomad4 FIN

AF:

0.0678

Gnomad4 NFE

AF:

0.0347

Gnomad4 OTH

AF:

0.0893

Alfa

AF:

0.0874

Hom.:

251

Bravo

AF:

0.114

Asia WGS

AF:

0.0540

AC:

187

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Mucopolysaccharidosis, MPS-III-A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00028

dbscSNV1_RF

Benign

0.17

SpliceAI score (max)

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over