rs139789664

Variant names:

• chr17-80205132-C-T
• rs139789664
• NM_001366385.1:c.2496C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-80205132-C-T
• chr17-80205132-C-A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001366385.1(CARD14):​c.2496C>T​(p.Leu832Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00516 in 1,613,754 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0052 (25 hom.)
• Consequence: CARD14 NM_001366385.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.520
• Publications: 4 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 17-80205132-C-T is Benign according to our data. Variant chr17-80205132-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 527887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.52 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00482 (734/152306) while in subpopulation NFE AF = 0.00601 (409/68028). AF 95% confidence interval is 0.00553. There are 1 homozygotes in GnomAd4. There are 315 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 734 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.2496C>T	p.Leu832Leu	synonymous	Exon 21 of 24	NP_001353314.1	Q9BXL6-1
	CARD14	NM_024110.4		c.2496C>T	p.Leu832Leu	synonymous	Exon 18 of 21	NP_077015.2	Q9BXL6-1
	CARD14	NR_047566.2		n.2633C>T		non_coding_transcript_exon	Exon 19 of 22

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	ENST00000648509.2	MANE Select	c.2496C>T	p.Leu832Leu	synonymous	Exon 21 of 24	ENSP00000498071.1	Q9BXL6-1
	CARD14	ENST00000344227.6	TSL:1	c.2496C>T	p.Leu832Leu	synonymous	Exon 18 of 21	ENSP00000344549.2	Q9BXL6-1
	CARD14	ENST00000651672.1		c.2523C>T	p.Leu841Leu	synonymous	Exon 20 of 23	ENSP00000499145.1	A0A494C1N2

Frequencies

GnomAD3 genomes AF: 0.00482 AC: 734 AN: 152188 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00463

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00485

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00603

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00376 AC: 942 AN: 250232 AF XY: 0.00356

Gnomad AFR exome AF: 0.00352

Gnomad AMR exome AF: 0.00316

Gnomad ASJ exome AF: 0.00439

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00242

Gnomad NFE exome AF: 0.00560

Gnomad OTH exome AF: 0.00279

GnomAD4 exome AF: 0.00520 AC: 7593 AN: 1461448 Hom.: 25 Cov.: 35 AF XY: 0.00506 AC XY: 3680 AN XY: 727066

African (AFR) AF: 0.00332 AC: 111 AN: 33478

American (AMR) AF: 0.00353 AC: 158 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00452 AC: 118 AN: 26110

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.000997 AC: 86 AN: 86254

European-Finnish (FIN) AF: 0.00269 AC: 143 AN: 53146

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5764

European-Non Finnish (NFE) AF: 0.00602 AC: 6689 AN: 1111920

Other (OTH) AF: 0.00467 AC: 282 AN: 60378

GnomAD4 genome AF: 0.00482 AC: 734 AN: 152306 Hom.: 1 Cov.: 32 AF XY: 0.00423 AC XY: 315 AN XY: 74478

African (AFR) AF: 0.00464 AC: 193 AN: 41570

American (AMR) AF: 0.00484 AC: 74 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00235 AC: 25 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00601 AC: 409 AN: 68028

Other (OTH) AF: 0.00711 AC: 15 AN: 2110

Alfa AF: 0.00529 Hom.: 1

Bravo AF: 0.00486

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00502

EpiControl AF: 0.00522

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Autoinflammatory syndrome (1)
-	-	1	not specified (1)
-	-	1	Pityriasis rubra pilaris;C1864497:Psoriasis 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_noAF	Benign	-0.38
CADD	Benign	2.4
DANN	Benign	0.91
PhyloP100		-0.52
Mutation Taster		=100/0	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: rs139789664; hg19: chr17-78178931; COSMIC: COSV100413290; COSMIC: COSV100413290;