Variant rs12294600 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145040.3(CAVIN3):c.763C>T(p.Leu255Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 1,537,122 control chromosomes in the GnomAD database, including 1,416 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.059 ( 695 hom., cov: 33)

Exomes 𝑓: 0.019 ( 721 hom. )

Consequence

CAVIN3
NM_145040.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.35

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:

LOC101927825 (HGNC:):

LOC101927825 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014595091).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAVIN3	NM_145040.3 linkuse as main transcript	c.763C>T	p.Leu255Phe	missense_variant	2/2	ENST00000303927.4
LOC101927825	XR_007062569.1 linkuse as main transcript	n.46G>A		non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAVIN3	ENST00000303927.4 linkuse as main transcript	c.763C>T	p.Leu255Phe	missense_variant	2/2	1	NM_145040.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0593

AC:

9020

AN:

152218

Hom.:

694

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0275

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00558

Gnomad FIN

AF:

0.0147

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0147

Gnomad OTH

AF:

0.0468

GnomAD3 exomes

AF:

0.0255

AC:

4753

AN:

186284

Hom.:

295

AF XY:

0.0218

AC XY:

2148

AN XY:

98446

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.0140

Gnomad ASJ exome

AF:

0.00846

Gnomad EAS exome

AF:

0.0000627

Gnomad SAS exome

AF:

0.00619

Gnomad FIN exome

AF:

0.0129

Gnomad NFE exome

AF:

0.0139

Gnomad OTH exome

AF:

0.0197

GnomAD4 exome

AF:

0.0188

AC:

25986

AN:

1384786

Hom.:

721

Cov.:

AF XY:

0.0182

AC XY:

12395

AN XY:

681818

show subpopulations

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.0160

Gnomad4 ASJ exome

AF:

0.00666

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00678

Gnomad4 FIN exome

AF:

0.0146

Gnomad4 NFE exome

AF:

0.0160

Gnomad4 OTH exome

AF:

0.0219

GnomAD4 genome

AF:

0.0594

AC:

9049

AN:

152336

Hom.:

695

Cov.:

AF XY:

0.0576

AC XY:

4291

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.176

Gnomad4 AMR

AF:

0.0274

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00517

Gnomad4 FIN

AF:

0.0147

Gnomad4 NFE

AF:

0.0147

Gnomad4 OTH

AF:

0.0464

Alfa

AF:

0.0233

Hom.:

334

Bravo

AF:

0.0669

TwinsUK

AF:

0.0186

AC:

ALSPAC

AF:

0.0156

AC:

ESP6500AA

AF:

0.176

AC:

774

ESP6500EA

AF:

0.0123

AC:

106

ExAC

AF:

0.0248

AC:

2993

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T

Eigen

Benign

0.033

Eigen_PC

Benign

0.011

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.47

T;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

P;P

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.71

N;N

REVEL

Benign

0.072

Sift

Uncertain

0.011

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.85

P;.

Vest4

0.39

MPC

0.55

ClinPred

0.016

GERP RS

5.1

Varity_R

0.11

gMVP

0.077

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over