chr17-80213874-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000199.5(SGSH):c.675C>T(p.Phe225Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,607,950 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 8 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 5 hom. )

Consequence

SGSH
NM_000199.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.284

Publications

3 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 -16 ACMG points.

BP6

Variant 17-80213874-G-A is Benign according to our data. Variant chr17-80213874-G-A is described in ClinVar as Benign. ClinVar VariationId is 528318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00538 (819/152342) while in subpopulation AFR AF = 0.0188 (782/41578). AF 95% confidence interval is 0.0177. There are 8 homozygotes in GnomAd4. There are 400 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AD,AR gene

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	HGVSp	Effect	Exon Rank	Protein	UniProt
SGSH	NM_000199.5	MANE Select	c.675C>T	p.Phe225Phe	synonymous	Exon 6 of 8	NP_000190.1	P51688
SGSH	NM_001352921.3		c.675C>T	p.Phe225Phe	synonymous	Exon 6 of 8	NP_001339850.1
SGSH	NM_001352922.2		c.675C>T	p.Phe225Phe	synonymous	Exon 6 of 9	NP_001339851.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SGSH	ENST00000326317.11	TSL:1 MANE Select	c.675C>T	p.Phe225Phe	synonymous	Exon 6 of 8	ENSP00000314606.6	P51688
SGSH	ENST00000575282.5	TSL:1	n.970C>T		non_coding_transcript_exon	Exon 5 of 5
SGSH	ENST00000570923.1	TSL:2	c.710C>T	p.Ser237Leu	missense	Exon 6 of 7	ENSP00000458200.1	I3L0M2

Frequencies

GnomAD3 genomes

AF:

0.00536

AC:

816

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00149

AC:

351

AN:

235912

AF XY:

0.00125

show subpopulations

Gnomad AFR exome

AF:

0.0197

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000942

Gnomad OTH exome

AF:

0.000521

GnomAD4 exome

AF:

0.000593

AC:

863

AN:

1455608

Hom.:

Cov.:

AF XY:

0.000492

AC XY:

356

AN XY:

724012

show subpopulations

African (AFR)

AF:

0.0191

AC:

640

AN:

33456

American (AMR)

AF:

0.00124

AC:

AN:

44228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25904

East Asian (EAS)

AF:

0.00

AC:

AN:

39532

South Asian (SAS)

AF:

0.0000468

AC:

AN:

85448

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49830

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000711

AC:

AN:

1111228

Other (OTH)

AF:

0.00126

AC:

AN:

60224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

143

190

238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00538

AC:

819

AN:

152342

Hom.:

Cov.:

AF XY:

0.00537

AC XY:

400

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0188

AC:

782

AN:

41578

American (AMR)

AF:

0.00111

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68038

Other (OTH)

AF:

0.00473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

124

166

207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00194

Hom.:

Bravo

AF:

0.00595

ESP6500AA

AF:

0.0155

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00164

AC:

198

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Mucopolysaccharidosis, MPS-III-A (4)

not provided (1)

SGSH-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.090

CADD

Benign

(source)

DANN

Benign

0.92

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0087

PhyloP100

0.28

Sift4G

Benign

0.26

Vest4

0.34

MVP

0.93

GERP RS

-0.016

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: -20

DS_AL_spliceai

0.20

Position offset: 11

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