17-80214155-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000575282.5(SGSH):n.689T>C variant causes a non coding transcript exon 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
ENST00000575282.5 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.10

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

familial pityriasis rubra pilaris
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
psoriasis 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

CARD14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 92612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGSH	NM_000199.5 link	c.663+17T>C		intron_variant	Intron 5 of 7	ENST00000326317.11	NP_000190.1	P51688

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGSH	ENST00000326317.11 link	c.663+17T>C		intron_variant	Intron 5 of 7	1	NM_000199.5	ENSP00000314606.6		P51688

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

GnomAD2 exomes

AF:

0.453

AC:

99668

AN:

220052

AF XY:

0.444

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 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

African (AFR)

AF:

0.613

AC:

20453

AN:

33340

American (AMR)

AF:

0.586

AC:

24467

AN:

41746

Ashkenazi Jewish (ASJ)

AF:

0.406

AC:

10445

AN:

25738

East Asian (EAS)

AF:

0.357

AC:

13984

AN:

39164

South Asian (SAS)

AF:

0.468

AC:

39430

AN:

84212

European-Finnish (FIN)

AF:

0.440

AC:

22497

AN:

51146

Middle Eastern (MID)

AF:

0.452

AC:

2600

AN:

5748

European-Non Finnish (NFE)

AF:

0.392

AC:

433745

AN:

1105868

Other (OTH)

AF:

0.429

AC:

25672

AN:

59850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

20924

41849

62773

83698

104622

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13682

27364

41046

54728

68410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.474

AC:

72031

AN:

152038

Hom.:

17748

Cov.:

AF XY:

0.475

AC XY:

35280

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.608

AC:

25200

AN:

41476

American (AMR)

AF:

0.545

AC:

8331

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.409

AC:

1420

AN:

3472

East Asian (EAS)

AF:

0.413

AC:

2126

AN:

5150

South Asian (SAS)

AF:

0.479

AC:

2307

AN:

4816

European-Finnish (FIN)

AF:

0.433

AC:

4580

AN:

10580

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.393

AC:

26723

AN:

67934

Other (OTH)

AF:

0.475

AC:

1005

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1956

3911

5867

7822

9778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

662

1324

1986

2648

3310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.307

Hom.:

4160

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

Aug 28, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mucopolysaccharidosis, MPS-III-A

Benign:4

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:4

Oct 22, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 22, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.27

(source)

DANN

Benign

0.33

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over