Variant 11-6319353-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_145040.3(CAVIN3):c.596C>T(p.Pro199Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,595,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

CAVIN3
NM_145040.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.760

Variant links:

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]

CAVIN3 links:

CAVIN3 (HGNC:):

CAVIN3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1380378).

BS2

High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAVIN3	NM_145040.3 linkuse as main transcript	c.596C>T	p.Pro199Leu	missense_variant	2/2	ENST00000303927.4	NP_659477.2	Q969G5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAVIN3	ENST00000303927.4 linkuse as main transcript	c.596C>T	p.Pro199Leu	missense_variant	2/2	1	NM_145040.3	ENSP00000307292.3		Q969G5

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000191

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000838

AC:

AN:

226800

Hom.:

AF XY:

0.0000807

AC XY:

AN XY:

123912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000134

AC:

194

AN:

1443340

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

717340

show subpopulations

Gnomad4 AFR exome

AF:

0.0000616

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000167

Gnomad4 OTH exome

AF:

0.000135

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000193

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000743

AC:

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

Nov 07, 2022

The c.596C>T (p.P199L) alteration is located in exon 2 (coding exon 2) of the PRKCDBP gene. This alteration results from a C to T substitution at nucleotide position 596, causing the proline (P) at amino acid position 199 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-0.012

Eigen_PC

Benign

0.027

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.043

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.77

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.83

N;N

REVEL

Benign

0.063

Sift

Uncertain

0.0030

D;D

Sift4G

Benign

0.061

T;D

Polyphen

0.83

P;.

Vest4

0.19

MVP

0.63

MPC

0.40

ClinPred

0.16

GERP RS

4.1

Varity_R

0.075

gMVP

0.11

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over