chr17-80206823-C-T

Variant names:

• chr17-80206823-C-T
• rs116354481
• NM_001366385.1:c.2692-147C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001366385.1(CARD14):​c.2692-147C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 457,236 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00048 (0 hom.)
• Consequence: CARD14 NM_001366385.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.150
• Publications: 0 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]

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-80206823-C-T is Benign according to our data. Variant chr17-80206823-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1202696.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00423 (644/152168) while in subpopulation AFR AF = 0.0143 (594/41520). AF 95% confidence interval is 0.0134. There are 4 homozygotes in GnomAd4. There are 273 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 644 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366385.1. 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.2692-147C>T		intron	N/A	NP_001353314.1	Q9BXL6-1
	CARD14	NM_024110.4		c.2692-147C>T		intron	N/A	NP_077015.2	Q9BXL6-1
	CARD14	NR_047566.2		n.2829-147C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	ENST00000648509.2	MANE Select	c.2692-147C>T		intron	N/A	ENSP00000498071.1	Q9BXL6-1
	CARD14	ENST00000344227.6	TSL:1	c.2692-147C>T		intron	N/A	ENSP00000344549.2	Q9BXL6-1
	CARD14	ENST00000651672.1		c.2719-147C>T		intron	N/A	ENSP00000499145.1	A0A494C1N2

Frequencies

GnomAD3 genomes AF: 0.00423 AC: 643 AN: 152050 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00479

GnomAD4 exome AF: 0.000479 AC: 146 AN: 305068 Hom.: 0 Cov.: 4 AF XY: 0.000398 AC XY: 63 AN XY: 158328

African (AFR) AF: 0.0131 AC: 102 AN: 7760

American (AMR) AF: 0.00162 AC: 15 AN: 9232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10128

East Asian (EAS) AF: 0.00 AC: 0 AN: 23574

South Asian (SAS) AF: 0.00 AC: 0 AN: 15656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30326

Middle Eastern (MID) AF: 0.000329 AC: 1 AN: 3042

European-Non Finnish (NFE) AF: 0.0000214 AC: 4 AN: 186692

Other (OTH) AF: 0.00129 AC: 24 AN: 18658

GnomAD4 genome AF: 0.00423 AC: 644 AN: 152168 Hom.: 4 Cov.: 33 AF XY: 0.00367 AC XY: 273 AN XY: 74390

African (AFR) AF: 0.0143 AC: 594 AN: 41520

American (AMR) AF: 0.00255 AC: 39 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67994

Other (OTH) AF: 0.00474 AC: 10 AN: 2110

Alfa AF: 0.00347 Hom.: 0

Bravo AF: 0.00484

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.35
DANN	Benign	0.58
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs116354481; hg19: chr17-78180622;