chr11-6319175-C-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_145040.3(CAVIN3):c.774G>C(p.Glu258Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,529,558 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 1 hom., cov: 33)
Exomes 𝑓: 0.000022 ( 0 hom. )
Consequence
CAVIN3
NM_145040.3 missense
NM_145040.3 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 0.0860
Genes affected
CAVIN3 (HGNC:9400): (caveolae associated protein 3) The protein encoded by this gene was identified as a binding protein of the protein kinase C, delta (PRKCD). The expression of this gene in cultured cell lines is strongly induced by serum starvation. The expression of this protein was found to be down-regulated in various cancer cell lines, suggesting the possible tumor suppressor function of this protein. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.048556536).
BS2
?
High AC in GnomAd at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAVIN3 | NM_145040.3 | c.774G>C | p.Glu258Asp | missense_variant | 2/2 | ENST00000303927.4 | |
LOC101927825 | XR_007062569.1 | n.35C>G | non_coding_transcript_exon_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAVIN3 | ENST00000303927.4 | c.774G>C | p.Glu258Asp | missense_variant | 2/2 | 1 | NM_145040.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152238Hom.: 1 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000496 AC: 9AN: 181504Hom.: 0 AF XY: 0.0000627 AC XY: 6AN XY: 95756
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GnomAD4 exome AF: 0.0000218 AC: 30AN: 1377202Hom.: 0 Cov.: 29 AF XY: 0.0000281 AC XY: 19AN XY: 677024
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152356Hom.: 1 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74502
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 07, 2023 | The c.774G>C (p.E258D) alteration is located in exon 2 (coding exon 2) of the PRKCDBP gene. This alteration results from a G to C substitution at nucleotide position 774, causing the glutamic acid (E) at amino acid position 258 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
T;T
Polyphen
P;.
Vest4
MutPred
Gain of loop (P = 0.0045);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at