Variant 17-80213921-A-G 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.664-36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,578,206 control chromosomes in the GnomAD database, including 98,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8173 hom., cov: 32)

Exomes 𝑓: 0.35 ( 90438 hom. )

Consequence

SGSH
NM_000199.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.09

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 17-80213921-A-G is Benign according to our data. Variant chr17-80213921-A-G is described in ClinVar as [Benign]. Clinvar id is 255517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.451 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.664-36T>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.664-36T>C		intron_variant		1	NM_000199.5	ENSP00000314606	P1

Frequencies

GnomAD3 genomes

AF:

0.319

AC:

48297

AN:

151552

Hom.:

8156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.199

Gnomad AMR

AF:

0.459

Gnomad ASJ

AF:

0.358

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.410

Gnomad FIN

AF:

0.356

Gnomad MID

AF:

0.331

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.352

GnomAD3 exomes

AF:

0.382

AC:

80792

AN:

211418

Hom.:

16013

AF XY:

0.378

AC XY:

43659

AN XY:

115442

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.546

Gnomad ASJ exome

AF:

0.361

Gnomad EAS exome

AF:

0.425

Gnomad SAS exome

AF:

0.410

Gnomad FIN exome

AF:

0.380

Gnomad NFE exome

AF:

0.344

Gnomad OTH exome

AF:

0.373

GnomAD4 exome

AF:

0.352

AC:

502464

AN:

1426538

Hom.:

90438

Cov.:

AF XY:

0.354

AC XY:

251253

AN XY:

709424

show subpopulations

Gnomad4 AFR exome

AF:

0.185

Gnomad4 AMR exome

AF:

0.537

Gnomad4 ASJ exome

AF:

0.360

Gnomad4 EAS exome

AF:

0.341

Gnomad4 SAS exome

AF:

0.405

Gnomad4 FIN exome

AF:

0.370

Gnomad4 NFE exome

AF:

0.346

Gnomad4 OTH exome

AF:

0.355

GnomAD4 genome

AF:

0.319

AC:

48343

AN:

151668

Hom.:

8173

Cov.:

AF XY:

0.322

AC XY:

23867

AN XY:

74102

show subpopulations

Gnomad4 AFR

AF:

0.195

Gnomad4 AMR

AF:

0.460

Gnomad4 ASJ

AF:

0.358

Gnomad4 EAS

AF:

0.399

Gnomad4 SAS

AF:

0.410

Gnomad4 FIN

AF:

0.356

Gnomad4 NFE

AF:

0.343

Gnomad4 OTH

AF:

0.353

Alfa

AF:

0.337

Hom.:

1599

Bravo

AF:

0.324

Asia WGS

AF:

0.394

AC:

1369

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mucopolysaccharidosis, MPS-III-A

Benign:2

Benign, criteria provided, single submitter	clinical testing	Counsyl	Feb 28, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.13

DANN

Benign

0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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