ENST00000575282.5:n.923T>C

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.923T>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 0.349 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
ENST00000575282.5 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.09

Publications

5 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=-0.9).

BP6

Variant 17-80213921-A-G is Benign according to our data. Variant chr17-80213921-A-G is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
SGSH	NM_000199.5 link	c.664-36T>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.664-36T>C		intron_variant	Intron 5 of 7	1	NM_000199.5	ENSP00000314606.6		P51688

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

GnomAD2 exomes

AF:

0.382

AC:

80792

AN:

211418

AF XY:

0.378

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 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

African (AFR)

AF:

0.185

AC:

6137

AN:

33180

American (AMR)

AF:

0.537

AC:

22161

AN:

41298

Ashkenazi Jewish (ASJ)

AF:

0.360

AC:

9208

AN:

25606

East Asian (EAS)

AF:

0.341

AC:

13288

AN:

39016

South Asian (SAS)

AF:

0.405

AC:

33766

AN:

83446

European-Finnish (FIN)

AF:

0.370

AC:

16148

AN:

43642

Middle Eastern (MID)

AF:

0.354

AC:

2023

AN:

5712

European-Non Finnish (NFE)

AF:

0.346

AC:

378644

AN:

1095248

Other (OTH)

AF:

0.355

AC:

21089

AN:

59390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

17920

35840

53761

71681

89601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12146

24292

36438

48584

60730

<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:

0.319

AC:

48343

AN:

151668

Hom.:

8173

Cov.:

AF XY:

0.322

AC XY:

23867

AN XY:

74102

show subpopulations

African (AFR)

AF:

0.195

AC:

8085

AN:

41438

American (AMR)

AF:

0.460

AC:

7000

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.358

AC:

1237

AN:

3456

East Asian (EAS)

AF:

0.399

AC:

2045

AN:

5120

South Asian (SAS)

AF:

0.410

AC:

1973

AN:

4808

European-Finnish (FIN)

AF:

0.356

AC:

3739

AN:

10516

Middle Eastern (MID)

AF:

0.345

AC:

100

AN:

290

European-Non Finnish (NFE)

AF:

0.343

AC:

23242

AN:

67808

Other (OTH)

AF:

0.353

AC:

741

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1660

3320

4981

6641

8301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<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:

0.337

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

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 28, 2017

Counsyl

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.13

(source)

DANN

Benign

0.37

PhyloP100

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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