11-6320181-G-C

Position:

• chr11-6320181-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145040.3(CAVIN3):​c.296C>G​(p.Ala99Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAVIN3 NM_145040.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.71

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAVIN3	NM_145040.3	c.296C>G	p.Ala99Gly	missense_variant	1/2	ENST00000303927.4	NP_659477.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAVIN3	ENST00000303927.4	c.296C>G	p.Ala99Gly	missense_variant	1/2	1	NM_145040.3	ENSP00000307292.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2024

The c.296C>G (p.A99G) alteration is located in exon 1 (coding exon 1) of the PRKCDBP gene. This alteration results from a C to G substitution at nucleotide position 296, causing the alanine (A) at amino acid position 99 to be replaced by a glycine (G). 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	0.26
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.75	T;T
M_CAP	Pathogenic	0.37	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.34	T
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0070	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.21
MutPred		0.28		Gain of relative solvent accessibility (P = 0.1259);Gain of relative solvent accessibility (P = 0.1259);
MVP		0.57
MPC		1.1
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.39
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-6341411;