GeneBe

NM_001366385.1:c.2476C>G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001366385.1(CARD14):​c.2476C>G​(p.Arg826Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R826Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CARD14
NM_001366385.1 missense

Scores

2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.700

Publications

1 publications found
Variant links:
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)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.103250265).

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.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
CARD14
NM_001366385.1
MANE Select
c.2476C>Gp.Arg826Gly
missense
Exon 21 of 24NP_001353314.1Q9BXL6-1
CARD14
NM_024110.4
c.2476C>Gp.Arg826Gly
missense
Exon 18 of 21NP_077015.2Q9BXL6-1
CARD14
NR_047566.2
n.2613C>G
non_coding_transcript_exon
Exon 19 of 22

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
CARD14
ENST00000648509.2
MANE Select
c.2476C>Gp.Arg826Gly
missense
Exon 21 of 24ENSP00000498071.1Q9BXL6-1
CARD14
ENST00000344227.6
TSL:1
c.2476C>Gp.Arg826Gly
missense
Exon 18 of 21ENSP00000344549.2Q9BXL6-1
CARD14
ENST00000651672.1
c.2503C>Gp.Arg835Gly
missense
Exon 20 of 23ENSP00000499145.1A0A494C1N2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000401
AC:
1
AN:
249504
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.0000622
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1461320
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
726998
African (AFR)
AF:
0.00
AC:
0
AN:
33476
American (AMR)
AF:
0.00
AC:
0
AN:
44700
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26104
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86248
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53092
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5746
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111884
Other (OTH)
AF:
0.00
AC:
0
AN:
60374
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000227
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
7.7
DANN
Benign
0.89
DEOGEN2
Benign
0.10
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.067
N
LIST_S2
Benign
0.39
T
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.3
M
PhyloP100
0.70
PrimateAI
Benign
0.29
T
PROVEAN
Uncertain
-3.3
D
REVEL
Benign
0.045
Sift
Benign
0.054
T
Sift4G
Benign
0.13
T
Polyphen
0.0
B
Vest4
0.14
MVP
0.45
MPC
0.19
ClinPred
0.073
T
GERP RS
1.6
Varity_R
0.11
gMVP
0.69

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

Publications

Other links and lift over

dbSNP: rs139467141; hg19: chr17-78178911; API