chr17-80202434-T-G

Variant names:

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

Variant summary

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

The NM_001257970.1(CARD14):​c.*10T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,604,998 control chromosomes in the GnomAD database, including 460 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (116 hom., cov: 31)
  • Exomes 𝑓: 0.015 (344 hom.)
• Consequence: CARD14 NM_001257970.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 17-80202434-T-G is Benign according to our data. Variant chr17-80202434-T-G is described in ClinVar as Benign. ClinVar VariationId is 1165098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0649 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>G		intron	N/A	NP_001353314.1	Q9BXL6-1
	CARD14	NM_001257970.1		c.*10T>G		3_prime_UTR	Exon 15 of 15	NP_001244899.1	Q9BXL6-2
	CARD14	NM_024110.4		c.2219+14T>G		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>G		3_prime_UTR	Exon 15 of 15	ENSP00000461806.1	Q9BXL6-2
	CARD14	ENST00000648509.2	MANE Select	c.2219+14T>G		intron	N/A	ENSP00000498071.1	Q9BXL6-1
	CARD14	ENST00000344227.6	TSL:1	c.2219+14T>G		intron	N/A	ENSP00000344549.2	Q9BXL6-1

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4379 AN: 151832 Hom.: 116 Cov.: 31

Gnomad AFR AF: 0.0668

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00467

Gnomad SAS AF: 0.0563

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0121

Gnomad OTH AF: 0.0283

GnomAD2 exomes AF: 0.0202 AC: 4956 AN: 245052 AF XY: 0.0211

Gnomad AFR exome AF: 0.0685

Gnomad AMR exome AF: 0.0103

Gnomad ASJ exome AF: 0.00372

Gnomad EAS exome AF: 0.00454

Gnomad FIN exome AF: 0.0101

Gnomad NFE exome AF: 0.0134

Gnomad OTH exome AF: 0.0160

GnomAD4 exome AF: 0.0147 AC: 21321 AN: 1453048 Hom.: 344 Cov.: 50 AF XY: 0.0157 AC XY: 11299 AN XY: 721350

African (AFR) AF: 0.0683 AC: 2280 AN: 33358

American (AMR) AF: 0.0112 AC: 498 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.00330 AC: 86 AN: 26054

East Asian (EAS) AF: 0.00271 AC: 107 AN: 39482

South Asian (SAS) AF: 0.0510 AC: 4391 AN: 86130

European-Finnish (FIN) AF: 0.0108 AC: 556 AN: 51418

Middle Eastern (MID) AF: 0.0173 AC: 98 AN: 5654

European-Non Finnish (NFE) AF: 0.0110 AC: 12214 AN: 1106348

Other (OTH) AF: 0.0182 AC: 1091 AN: 60012

GnomAD4 genome AF: 0.0289 AC: 4397 AN: 151950 Hom.: 116 Cov.: 31 AF XY: 0.0283 AC XY: 2101 AN XY: 74274

African (AFR) AF: 0.0670 AC: 2777 AN: 41442

American (AMR) AF: 0.0204 AC: 312 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.00468 AC: 24 AN: 5132

South Asian (SAS) AF: 0.0572 AC: 275 AN: 4808

European-Finnish (FIN) AF: 0.0101 AC: 107 AN: 10576

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0121 AC: 825 AN: 67926

Other (OTH) AF: 0.0280 AC: 59 AN: 2110

Alfa AF: 0.00833 Hom.: 1729

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Pityriasis rubra pilaris;C1864497:Psoriasis 2 (2)
-	-	1	CARD14-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.43
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;