rs34029730

Variant names:

• chr17-80213922-CAG-C
• rs34029730
• NM_000199.5:c.664-39_664-38delCT

Your query was ambiguous. Multiple possible variants found:

• chr17-80213922-CAG-C
• chr17-80213922-CAG-CAGAG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000199.5(SGSH):​c.664-39_664-38delCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,577,990 control chromosomes in the GnomAD database, including 98,466 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8175 hom., cov: 0)
  • Exomes 𝑓: 0.35 (90291 hom.)
• Consequence: SGSH NM_000199.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.504
• Publications: 5 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 17-80213922-CAG-C is Benign according to our data. Variant chr17-80213922-CAG-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255518.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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGSH	NM_000199.5	MANE Select	c.664-39_664-38delCT		intron	N/A	NP_000190.1	P51688
	SGSH	NM_001352921.3		c.664-39_664-38delCT		intron	N/A	NP_001339850.1
	SGSH	NM_001352922.2		c.664-39_664-38delCT		intron	N/A	NP_001339851.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGSH	ENST00000326317.11	TSL:1 MANE Select	c.664-39_664-38delCT		intron	N/A	ENSP00000314606.6	P51688
	SGSH	ENST00000575282.5	TSL:1	n.920_921delCT		non_coding_transcript_exon	Exon 5 of 5
	SGSH	ENST00000874335.1		c.664-39_664-38delCT		intron	N/A	ENSP00000544394.1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48304 AN: 151612 Hom.: 8158 Cov.: 0

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.352

GnomAD2 exomes AF: 0.382 AC: 80474 AN: 210600 AF XY: 0.378

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: 0.381

Gnomad NFE exome AF: 0.344

Gnomad OTH exome AF: 0.373

GnomAD4 exome AF: 0.352 AC: 501882 AN: 1426262 Hom.: 90291 AF XY: 0.354 AC XY: 250982 AN XY: 709416

African (AFR) AF: 0.185 AC: 6136 AN: 33180

American (AMR) AF: 0.535 AC: 22075 AN: 41266

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 9192 AN: 25588

East Asian (EAS) AF: 0.340 AC: 13279 AN: 39008

South Asian (SAS) AF: 0.404 AC: 33729 AN: 83404

European-Finnish (FIN) AF: 0.369 AC: 16094 AN: 43566

Middle Eastern (MID) AF: 0.354 AC: 2018 AN: 5706

European-Non Finnish (NFE) AF: 0.345 AC: 378285 AN: 1095140

Other (OTH) AF: 0.355 AC: 21074 AN: 59404

GnomAD4 genome AF: 0.319 AC: 48350 AN: 151728 Hom.: 8175 Cov.: 0 AF XY: 0.322 AC XY: 23870 AN XY: 74124

African (AFR) AF: 0.195 AC: 8087 AN: 41470

American (AMR) AF: 0.460 AC: 7001 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1239 AN: 3458

East Asian (EAS) AF: 0.400 AC: 2046 AN: 5120

South Asian (SAS) AF: 0.410 AC: 1973 AN: 4808

European-Finnish (FIN) AF: 0.355 AC: 3741 AN: 10530

Middle Eastern (MID) AF: 0.345 AC: 100 AN: 290

European-Non Finnish (NFE) AF: 0.343 AC: 23240 AN: 67814

Other (OTH) AF: 0.353 AC: 742 AN: 2100

Alfa AF: 0.337 Hom.: 1599

Bravo AF: 0.324

Asia WGS AF: 0.394 AC: 1369 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Mucopolysaccharidosis, MPS-III-A (2)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34029730; hg19: chr17-78187721; COSMIC: COSV58339027; COSMIC: COSV58339027;