rs34029730

chr17-80213922-CAG-Cchr17-80213922-CAG-CAGAG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000199.5(SGSH):c.664-39_664-38del 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 1,577,990 control chromosomes in the GnomAD database, including 98,466 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8175 hom., cov: 0)
  • Exomes 𝑓: 0.35 (90291 hom.)
• Consequence: SGSH NM_000199.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.504

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]

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 17-80213922-CAG-C is Benign according to our data. Variant chr17-80213922-CAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 255518.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	UniProt
SGSH	NM_000199.5	c.664-39_664-38del		intron_variant		ENST00000326317.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGSH	ENST00000326317.11	c.664-39_664-38del		intron_variant		1	NM_000199.5	P1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48304 AN: 151612 Hom.: 8158 Cov.: 0

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.352

GnomAD3 exomes AF: 0.382 AC: 80474 AN: 210600 Hom.: 15931 AF XY: 0.378 AC XY: 43494 AN XY: 115040

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: 0.411

Gnomad FIN exome AF: 0.381

Gnomad NFE exome AF: 0.344

Gnomad OTH exome AF: 0.373

GnomAD4 exome AF: 0.352 AC: 501882 AN: 1426262 Hom.: 90291 AF XY: 0.354 AC XY: 250982 AN XY: 709416

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.535

Gnomad4 ASJ exome AF: 0.359

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.404

Gnomad4 FIN exome AF: 0.369

Gnomad4 NFE exome AF: 0.345

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.319 AC: 48350 AN: 151728 Hom.: 8175 Cov.: 0 AF XY: 0.322 AC XY: 23870 AN XY: 74124

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.355

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/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Mucopolysaccharidosis, MPS-III-A Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 27, 2019	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs34029730; hg19: chr17-78187721;