rs4889839

Variant names:

• chr17-80215164-G-A
• rs4889839
• NM_000199.5:c.250-26C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-80215164-G-A
• chr17-80215164-G-C
• chr17-80215164-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000199.5(SGSH):​c.250-26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 1,581,696 control chromosomes in the GnomAD database, including 212,596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (22858 hom., cov: 33)
  • Exomes 𝑓: 0.51 (189738 hom.)
• Consequence: SGSH NM_000199.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.35
• Publications: 15 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: 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 17-80215164-G-A is Benign according to our data. Variant chr17-80215164-G-A is described in ClinVar as Benign. ClinVar VariationId is 255515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 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.250-26C>T		intron	N/A	NP_000190.1
	SGSH	NM_001352921.3		c.250-26C>T		intron	N/A	NP_001339850.1
	SGSH	NM_001352922.2		c.250-26C>T		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.250-26C>T		intron	N/A	ENSP00000314606.6
	SGSH	ENST00000575282.5	TSL:1	n.259-26C>T		intron	N/A
	SGSH	ENST00000874335.1		c.250-26C>T		intron	N/A	ENSP00000544394.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82690 AN: 151962 Hom.: 22837 Cov.: 33

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.533

GnomAD2 exomes AF: 0.510 AC: 119007 AN: 233552 AF XY: 0.513

Gnomad AFR exome AF: 0.650

Gnomad AMR exome AF: 0.390

Gnomad ASJ exome AF: 0.487

Gnomad EAS exome AF: 0.600

Gnomad FIN exome AF: 0.501

Gnomad NFE exome AF: 0.512

Gnomad OTH exome AF: 0.520

GnomAD4 exome AF: 0.513 AC: 733659 AN: 1429616 Hom.: 189738 Cov.: 27 AF XY: 0.513 AC XY: 365816 AN XY: 712466

African (AFR) AF: 0.661 AC: 21762 AN: 32902

American (AMR) AF: 0.395 AC: 17365 AN: 43934

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 12556 AN: 25926

East Asian (EAS) AF: 0.675 AC: 26522 AN: 39278

South Asian (SAS) AF: 0.523 AC: 44604 AN: 85366

European-Finnish (FIN) AF: 0.497 AC: 22693 AN: 45698

Middle Eastern (MID) AF: 0.554 AC: 3171 AN: 5724

European-Non Finnish (NFE) AF: 0.508 AC: 554156 AN: 1091370

Other (OTH) AF: 0.519 AC: 30830 AN: 59418

GnomAD4 genome AF: 0.544 AC: 82751 AN: 152080 Hom.: 22858 Cov.: 33 AF XY: 0.543 AC XY: 40339 AN XY: 74354

African (AFR) AF: 0.647 AC: 26844 AN: 41484

American (AMR) AF: 0.446 AC: 6814 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1651 AN: 3470

East Asian (EAS) AF: 0.615 AC: 3167 AN: 5152

South Asian (SAS) AF: 0.522 AC: 2514 AN: 4818

European-Finnish (FIN) AF: 0.509 AC: 5394 AN: 10592

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34498 AN: 67958

Other (OTH) AF: 0.533 AC: 1126 AN: 2112

Alfa AF: 0.518 Hom.: 41700

Bravo AF: 0.544

Asia WGS AF: 0.567 AC: 1971 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Mucopolysaccharidosis, MPS-III-A (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.046
DANN	Benign	0.77
PhyloP100		-3.3
PromoterAI		0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4889839; hg19: chr17-78188963;