rs79407194

Variant names:

• chr17-80201809-C-T
• rs79407194
• NM_001366385.1:c.1917C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001366385.1(CARD14):​c.1917C>T​(p.Ala639Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,613,940 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00095 (6 hom.)
• Consequence: CARD14 NM_001366385.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.41
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 17-80201809-C-T is Benign according to our data. Variant chr17-80201809-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 458091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.41 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00317 (482/152278) while in subpopulation AFR AF = 0.00871 (362/41552). AF 95% confidence interval is 0.00797. There are 1 homozygotes in GnomAd4. There are 231 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 482 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.1917C>T	p.Ala639Ala	synonymous	Exon 17 of 24	NP_001353314.1	Q9BXL6-1
	CARD14	NM_024110.4		c.1917C>T	p.Ala639Ala	synonymous	Exon 14 of 21	NP_077015.2	Q9BXL6-1
	CARD14	NM_001257970.1		c.1917C>T	p.Ala639Ala	synonymous	Exon 14 of 15	NP_001244899.1	Q9BXL6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	ENST00000648509.2	MANE Select	c.1917C>T	p.Ala639Ala	synonymous	Exon 17 of 24	ENSP00000498071.1	Q9BXL6-1
	CARD14	ENST00000344227.6	TSL:1	c.1917C>T	p.Ala639Ala	synonymous	Exon 14 of 21	ENSP00000344549.2	Q9BXL6-1
	CARD14	ENST00000570421.5	TSL:1	c.1917C>T	p.Ala639Ala	synonymous	Exon 14 of 15	ENSP00000461806.1	Q9BXL6-2

Frequencies

GnomAD3 genomes AF: 0.00317 AC: 483 AN: 152160 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00876

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00152 AC: 383 AN: 251256 AF XY: 0.00123

Gnomad AFR exome AF: 0.00966

Gnomad AMR exome AF: 0.00182

Gnomad ASJ exome AF: 0.00675

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000651

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.000952 AC: 1392 AN: 1461662 Hom.: 6 Cov.: 33 AF XY: 0.000928 AC XY: 675 AN XY: 727158

African (AFR) AF: 0.00944 AC: 316 AN: 33474

American (AMR) AF: 0.00165 AC: 74 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00635 AC: 166 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000185 AC: 16 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.0180 AC: 104 AN: 5768

European-Non Finnish (NFE) AF: 0.000515 AC: 573 AN: 1111852

Other (OTH) AF: 0.00235 AC: 142 AN: 60392

GnomAD4 genome AF: 0.00317 AC: 482 AN: 152278 Hom.: 1 Cov.: 32 AF XY: 0.00310 AC XY: 231 AN XY: 74460

African (AFR) AF: 0.00871 AC: 362 AN: 41552

American (AMR) AF: 0.00255 AC: 39 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00835 AC: 29 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68002

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00200 Hom.: 0

Bravo AF: 0.00365

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00109

EpiControl AF: 0.00142

ClinVar

ClinVar submissions

Significance: Benign/Likely 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	Autoinflammatory syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.7
DANN	Benign	0.83
PhyloP100		-3.4
Mutation Taster		=97/3	polymorphism

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: rs79407194; hg19: chr17-78175608;