rs8069255

Variant names:

• chr17-80202434-T-A
• rs8069255
• ENST00000570421.5:c.*10T>A

Your query was ambiguous. Multiple possible variants found:

• chr17-80202434-T-A
• chr17-80202434-T-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001257970.1(CARD14):​c.*10T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,604,700 control chromosomes in the GnomAD database, including 184,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.40 (13277 hom., cov: 31)
  • Exomes 𝑓: 0.48 (170894 hom.)
• Consequence: CARD14 NM_001257970.1 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:7
• Conservation: PhyloP100: -3.42
• Publications: 14 publications found

Genes affected

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]

ENSG00000262580 (HGNC:):

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 Gene-Disease associations (from GenCC):

• mucopolysaccharidosis type 3A

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Myriad Women’s Health, PanelApp Australia, Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 17-80202434-T-A is Benign according to our data. Variant chr17-80202434-T-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 402482.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257970.1. 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
	CARD14	NM_001366385.1	MANE Select	c.2219+14T>A		intron	N/A	NP_001353314.1	Q9BXL6-1
	CARD14	NM_001257970.1		c.*10T>A		3_prime_UTR	Exon 15 of 15	NP_001244899.1	Q9BXL6-2
	CARD14	NM_024110.4		c.2219+14T>A		intron	N/A	NP_077015.2	Q9BXL6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	ENST00000570421.5	TSL:1	c.*10T>A		3_prime_UTR	Exon 15 of 15	ENSP00000461806.1	Q9BXL6-2
	CARD14	ENST00000648509.2	MANE Select	c.2219+14T>A		intron	N/A	ENSP00000498071.1	Q9BXL6-1
	CARD14	ENST00000344227.6	TSL:1	c.2219+14T>A		intron	N/A	ENSP00000344549.2	Q9BXL6-1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61389 AN: 151768 Hom.: 13278 Cov.: 31

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.402

GnomAD2 exomes AF: 0.414 AC: 101338 AN: 245052 AF XY: 0.421

Gnomad AFR exome AF: 0.246

Gnomad AMR exome AF: 0.265

Gnomad ASJ exome AF: 0.423

Gnomad EAS exome AF: 0.470

Gnomad FIN exome AF: 0.426

Gnomad NFE exome AF: 0.494

Gnomad OTH exome AF: 0.443

GnomAD4 exome AF: 0.479 AC: 695715 AN: 1452814 Hom.: 170894 Cov.: 50 AF XY: 0.476 AC XY: 342982 AN XY: 721196

African (AFR) AF: 0.246 AC: 8216 AN: 33360

American (AMR) AF: 0.275 AC: 12245 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 10976 AN: 26052

East Asian (EAS) AF: 0.550 AC: 21730 AN: 39478

South Asian (SAS) AF: 0.336 AC: 28937 AN: 86126

European-Finnish (FIN) AF: 0.431 AC: 22156 AN: 51360

Middle Eastern (MID) AF: 0.413 AC: 2335 AN: 5654

European-Non Finnish (NFE) AF: 0.508 AC: 561855 AN: 1106194

Other (OTH) AF: 0.454 AC: 27265 AN: 60002

GnomAD4 genome AF: 0.404 AC: 61394 AN: 151886 Hom.: 13277 Cov.: 31 AF XY: 0.400 AC XY: 29687 AN XY: 74240

African (AFR) AF: 0.254 AC: 10511 AN: 41426

American (AMR) AF: 0.337 AC: 5151 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1432 AN: 3468

East Asian (EAS) AF: 0.500 AC: 2562 AN: 5126

South Asian (SAS) AF: 0.323 AC: 1550 AN: 4804

European-Finnish (FIN) AF: 0.431 AC: 4550 AN: 10564

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34032 AN: 67906

Other (OTH) AF: 0.402 AC: 848 AN: 2110

Alfa AF: 0.373 Hom.: 1729

Bravo AF: 0.400

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	1	1	Pityriasis rubra pilaris (2)
-	-	1	Pityriasis rubra pilaris;C1864497:Psoriasis 2 (1)
-	-	1	Psoriasis 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.26
PhyloP100		-3.4
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: rs8069255; hg19: chr17-78176233; COSMIC: COSV60122323; COSMIC: COSV60122323;