17-80214155-A-G

Position:

chr17-80214155-A-G

Variant summary

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

The ENST00000326317.11(SGSH):c.663+17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,598,850 control chromosomes in the GnomAD database, including 141,640 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17748 hom., cov: 32)

Exomes 𝑓: 0.41 ( 123892 hom. )

Consequence

SGSH
ENST00000326317.11 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -1.10

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:

CARD14 (HGNC:16446): (caspase recruitment domain family member 14) This gene encodes a caspase recruitment domain-containing protein that is a member of the membrane-associated guanylate kinase (MAGUK) family of proteins. Members of this protein family are scaffold proteins that are involved in a diverse array of cellular processes including cellular adhesion, signal transduction and cell polarity control. This protein has been shown to specifically interact with BCL10, a protein known to function as a positive regulator of cell apoptosis and NF-kappaB activation. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]

CARD14 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=-0.88).

BP6

Variant 17-80214155-A-G is Benign according to our data. Variant chr17-80214155-A-G is described in ClinVar as [Benign]. Clinvar id is 92612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80214155-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 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.663+17T>C		intron_variant		ENST00000326317.11	NP_000190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGSH	ENST00000326317.11 linkuse as main transcript	c.663+17T>C		intron_variant		1	NM_000199.5	ENSP00000314606	P1

Frequencies

GnomAD3 genomes

AF:

0.473

AC:

71932

AN:

151920

Hom.:

17709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.608

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.544

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.413

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.393

Gnomad OTH

AF:

0.476

GnomAD3 exomes

AF:

0.453

AC:

99668

AN:

220052

Hom.:

23215

AF XY:

0.444

AC XY:

53127

AN XY:

119718

show subpopulations

Gnomad AFR exome

AF:

0.608

Gnomad AMR exome

AF:

0.593

Gnomad ASJ exome

AF:

0.405

Gnomad EAS exome

AF:

0.429

Gnomad SAS exome

AF:

0.473

Gnomad FIN exome

AF:

0.440

Gnomad NFE exome

AF:

0.392

Gnomad OTH exome

AF:

0.437

GnomAD4 exome

AF:

0.410

AC:

593293

AN:

1446812

Hom.:

123892

Cov.:

AF XY:

0.411

AC XY:

295350

AN XY:

718474

show subpopulations

Gnomad4 AFR exome

AF:

0.613

Gnomad4 AMR exome

AF:

0.586

Gnomad4 ASJ exome

AF:

0.406

Gnomad4 EAS exome

AF:

0.357

Gnomad4 SAS exome

AF:

0.468

Gnomad4 FIN exome

AF:

0.440

Gnomad4 NFE exome

AF:

0.392

Gnomad4 OTH exome

AF:

0.429

GnomAD4 genome

AF:

0.474

AC:

72031

AN:

152038

Hom.:

17748

Cov.:

AF XY:

0.475

AC XY:

35280

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.608

Gnomad4 AMR

AF:

0.545

Gnomad4 ASJ

AF:

0.409

Gnomad4 EAS

AF:

0.413

Gnomad4 SAS

AF:

0.479

Gnomad4 FIN

AF:

0.433

Gnomad4 NFE

AF:

0.393

Gnomad4 OTH

AF:

0.475

Alfa

AF:

0.361

Hom.:

2183

Bravo

AF:

0.489

Asia WGS

AF:

0.459

AC:

1596

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 28, 2017	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Mucopolysaccharidosis, MPS-III-A

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 22, 2016	Variant summary: The SGSH c.663+17T>C variant involves the alteration of a non-conserved intronic nucleotide with 5/5 splice prediction tools predicting no significant impact on splicing. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 40694/78358 (9033 homozygotes) at a frequency of 0.5193343, which suggests that the variant of interest is the major allele (allele most commonly observed in the general population). A reputable clinical laboratory cites the variant as "benign." Therefore, the variant of interest has been classified as Benign. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 22, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.27

DANN

Benign

0.33

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

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