rs4889839

chr17-80215164-G-Achr17-80215164-G-Cchr17-80215164-G-T

Variant summary

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

The NM_000199.5(SGSH):c.250-26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 1,581,696 control chromosomes in the GnomAD database, including 212,596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 22858 hom., cov: 33)

Exomes 𝑓: 0.51 ( 189738 hom. )

Consequence

SGSH
NM_000199.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.35

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=-1.02).

BP6

Variant 17-80215164-G-A is Benign according to our data. Variant chr17-80215164-G-A is described in ClinVar as [Benign]. Clinvar id is 255515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80215164-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGSH	NM_000199.5 linkuse as main transcript	c.250-26C>T		intron_variant		ENST00000326317.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGSH	ENST00000326317.11 linkuse as main transcript	c.250-26C>T		intron_variant		1	NM_000199.5	P1

Frequencies

GnomAD3 genomes

AF:

0.544

AC:

82690

AN:

151962

Hom.:

22837

Cov.:

show subpopulations

Gnomad AFR

AF:

0.647

Gnomad AMI

AF:

0.639

Gnomad AMR

AF:

0.447

Gnomad ASJ

AF:

0.476

Gnomad EAS

AF:

0.614

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.509

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.508

Gnomad OTH

AF:

0.533

GnomAD3 exomes

AF:

0.510

AC:

119007

AN:

233552

Hom.:

30573

AF XY:

0.513

AC XY:

65535

AN XY:

127680

show subpopulations

Gnomad AFR exome

AF:

0.650

Gnomad AMR exome

AF:

0.390

Gnomad ASJ exome

AF:

0.487

Gnomad EAS exome

AF:

0.600

Gnomad SAS exome

AF:

0.519

Gnomad FIN exome

AF:

0.501

Gnomad NFE exome

AF:

0.512

Gnomad OTH exome

AF:

0.520

GnomAD4 exome

AF:

0.513

AC:

733659

AN:

1429616

Hom.:

189738

Cov.:

AF XY:

0.513

AC XY:

365816

AN XY:

712466

show subpopulations

Gnomad4 AFR exome

AF:

0.661

Gnomad4 AMR exome

AF:

0.395

Gnomad4 ASJ exome

AF:

0.484

Gnomad4 EAS exome

AF:

0.675

Gnomad4 SAS exome

AF:

0.523

Gnomad4 FIN exome

AF:

0.497

Gnomad4 NFE exome

AF:

0.508

Gnomad4 OTH exome

AF:

0.519

GnomAD4 genome

AF:

0.544

AC:

82751

AN:

152080

Hom.:

22858

Cov.:

AF XY:

0.543

AC XY:

40339

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.647

Gnomad4 AMR

AF:

0.446

Gnomad4 ASJ

AF:

0.476

Gnomad4 EAS

AF:

0.615

Gnomad4 SAS

AF:

0.522

Gnomad4 FIN

AF:

0.509

Gnomad4 NFE

AF:

0.508

Gnomad4 OTH

AF:

0.533

Alfa

AF:

0.497

Hom.:

11553

Bravo

AF:

0.544

Asia WGS

AF:

0.567

AC:

1971

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 22, 2015	- -
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

- -

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

-1.0

Cadd

Benign

0.046

Dann

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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