rs117217614

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_000199.5(SGSH):c.664-50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.041 in 1,535,482 control chromosomes in the GnomAD database, including 1,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 122 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1370 hom. )

Consequence

SGSH
NM_000199.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.183

Publications

0 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet
psoriasis 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P

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=-0.92).

BP6

Variant 17-80213935-C-T is Benign according to our data. Variant chr17-80213935-C-T is described in ClinVar as Benign. ClinVar VariationId is 255519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0721 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000199.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SGSH	NM_000199.5	MANE Select	c.664-50G>A	intron	N/A	NP_000190.1	P51688
SGSH	NM_001352921.3		c.664-50G>A	intron	N/A	NP_001339850.1
SGSH	NM_001352922.2		c.664-50G>A	intron	N/A	NP_001339851.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SGSH	ENST00000326317.11	TSL:1 MANE Select	c.664-50G>A	intron	N/A	ENSP00000314606.6	P51688
SGSH	ENST00000575282.5	TSL:1	n.909G>A	non_coding_transcript_exon	Exon 5 of 5
SGSH	ENST00000874335.1		c.664-50G>A	intron	N/A	ENSP00000544394.1

Frequencies

GnomAD3 genomes

AF:

0.0333

AC:

5067

AN:

152054

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00891

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.0335

Gnomad ASJ

AF:

0.0796

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00622

Gnomad FIN

AF:

0.0610

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0450

Gnomad OTH

AF:

0.0460

GnomAD2 exomes

AF:

0.0350

AC:

6709

AN:

191950

AF XY:

0.0349

show subpopulations

Gnomad AFR exome

AF:

0.00734

Gnomad AMR exome

AF:

0.0263

Gnomad ASJ exome

AF:

0.0747

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0584

Gnomad NFE exome

AF:

0.0477

Gnomad OTH exome

AF:

0.0501

GnomAD4 exome

AF:

0.0419

AC:

57965

AN:

1383310

Hom.:

1370

Cov.:

AF XY:

0.0412

AC XY:

28389

AN XY:

688266

show subpopulations

African (AFR)

AF:

0.00778

AC:

253

AN:

32514

American (AMR)

AF:

0.0283

AC:

1093

AN:

38666

Ashkenazi Jewish (ASJ)

AF:

0.0720

AC:

1818

AN:

25266

East Asian (EAS)

AF:

0.00

AC:

AN:

38618

South Asian (SAS)

AF:

0.00796

AC:

649

AN:

81562

European-Finnish (FIN)

AF:

0.0563

AC:

2297

AN:

40822

Middle Eastern (MID)

AF:

0.0782

AC:

440

AN:

5630

European-Non Finnish (NFE)

AF:

0.0461

AC:

48978

AN:

1062192

Other (OTH)

AF:

0.0420

AC:

2437

AN:

58040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

2865

5730

8595

11460

14325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1828

3656

5484

7312

9140

<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:

0.0333

AC:

5061

AN:

152172

Hom.:

122

Cov.:

AF XY:

0.0330

AC XY:

2452

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.00889

AC:

369

AN:

41522

American (AMR)

AF:

0.0334

AC:

511

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0796

AC:

276

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00643

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0610

AC:

646

AN:

10598

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0450

AC:

3060

AN:

67996

Other (OTH)

AF:

0.0455

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

241

481

722

962

1203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0296

Hom.:

Bravo

AF:

0.0312

Asia WGS

AF:

0.00866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Mucopolysaccharidosis, MPS-III-A (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.39

(source)

DANN

Benign

0.72

PhyloP100

-0.18

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)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over