chr11-6319186-G-A

Variant names:

• chr11-6319186-G-A
• rs12294600
• NM_145040.3:c.763C>T

Variant summary

Our verdict is Benign. The variant received -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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145040.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN3	NM_145040.3	MANE Select	c.763C>T	p.Leu255Phe	missense	Exon 2 of 2	NP_659477.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN3	ENST00000303927.4	TSL:1 MANE Select	c.763C>T	p.Leu255Phe	missense	Exon 2 of 2	ENSP00000307292.3
	CAVIN3	ENST00000530979.1	TSL:2	c.859C>T	p.Leu287Phe	missense	Exon 3 of 3	ENSP00000432047.1
	CAVIN3	ENST00000524852.1	TSL:3	n.549C>T		non_coding_transcript_exon	Exon 2 of 2

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

GnomAD2 exomes AF: 0.0255 AC: 4753 AN: 186284 AF XY: 0.0218

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 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

African (AFR) AF: 0.180 AC: 5523 AN: 30666

American (AMR) AF: 0.0160 AC: 502 AN: 31300

Ashkenazi Jewish (ASJ) AF: 0.00666 AC: 137 AN: 20556

East Asian (EAS) AF: 0.00 AC: 0 AN: 38990

South Asian (SAS) AF: 0.00678 AC: 492 AN: 72534

European-Finnish (FIN) AF: 0.0146 AC: 738 AN: 50542

Middle Eastern (MID) AF: 0.0101 AC: 54 AN: 5362

European-Non Finnish (NFE) AF: 0.0160 AC: 17290 AN: 1077870

Other (OTH) AF: 0.0219 AC: 1250 AN: 56966

GnomAD4 genome AF: 0.0594 AC: 9049 AN: 152336 Hom.: 695 Cov.: 33 AF XY: 0.0576 AC XY: 4291 AN XY: 74500

African (AFR) AF: 0.176 AC: 7322 AN: 41560

American (AMR) AF: 0.0274 AC: 420 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00517 AC: 25 AN: 4832

European-Finnish (FIN) AF: 0.0147 AC: 156 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0147 AC: 999 AN: 68032

Other (OTH) AF: 0.0464 AC: 98 AN: 2114

Alfa AF: 0.0283 Hom.: 941

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 v4.9

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
Eigen	Benign	0.033
Eigen_PC	Benign	0.011
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.3
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.072
Sift	Uncertain	0.011	D
Sift4G	Pathogenic	0.0	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
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12294600; hg19: chr11-6340416;