rs12294600

Positions:

• chr11-6319186-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.059 (695 hom., cov: 33)
  • Exomes 𝑓: 0.019 (721 hom.)
• Consequence: CAVIN3 NM_145040.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35

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]

ENSG00000282556 (HGNC:):

ACMG classification

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	Protein	UniProt
CAVIN3	NM_145040.3	c.763C>T	p.Leu255Phe	missense_variant	2/2	ENST00000303927.4	NP_659477.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAVIN3	ENST00000303927.4	c.763C>T	p.Leu255Phe	missense_variant	2/2	1	NM_145040.3	ENSP00000307292.3

Frequencies

GnomAD3 genomes AF: 0.0593 AC: 9020 AN: 152218 Hom.: 694 Cov.: 33

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

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.: 29 AF XY: 0.0182 AC XY: 12395 AN XY: 681818

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.: 33 AF XY: 0.0576 AC XY: 4291 AN XY: 74500

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: 69

ALSPAC AF: 0.0156 AC: 60

ESP6500AA AF: 0.176 AC: 774

ESP6500EA AF: 0.0123 AC: 106

ExAC AF: 0.0248 AC: 2993

Asia WGS AF: 0.0120 AC: 40 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	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T
Eigen	Benign	0.033
Eigen_PC	Benign	0.011
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.47	T;T
MetaRNN	Benign	0.0015	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.41	T
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	T
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

Other links and lift over

dbSNP: rs12294600; hg19: chr11-6340416;