11-6319323-G-T

Variant names:

• chr11-6319323-G-T
• rs543801330
• NM_145040.3:c.626C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145040.3(CAVIN3):​c.626C>A​(p.Pro209Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CAVIN3 NM_145040.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28737226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAVIN3	NM_145040.3	c.626C>A	p.Pro209Gln	missense_variant	Exon 2 of 2	ENST00000303927.4	NP_659477.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAVIN3	ENST00000303927.4	c.626C>A	p.Pro209Gln	missense_variant	Exon 2 of 2	1	NM_145040.3	ENSP00000307292.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000426 AC: 1 AN: 234942 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 128254

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000310

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451842 Hom.: 0 Cov.: 67 AF XY: 0.00 AC XY: 0 AN XY: 721834

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000234

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.53	T
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.020	N;N
REVEL	Benign	0.20
Sift	Uncertain	0.0050	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.54
MutPred		0.15		Loss of catalytic residue at P209 (P = 0.0152);.;
MVP		0.67
MPC		1.1
ClinPred		0.88	D
GERP RS		5.1
Varity_R		0.26
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs543801330; hg19: chr11-6340553;