rs11544766

chr11-6320274-C-Gchr11-6320274-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_145040.3(CAVIN3):c.203G>C(p.Ser68Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000517 in 1,565,872 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.0027 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00028 (1 hom.)
• Consequence: CAVIN3 NM_145040.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.868

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008076578).
• BS2: High AC in GnomAd at 413 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAVIN3	NM_145040.3	c.203G>C	p.Ser68Thr	missense_variant	1/2	ENST00000303927.4
LOC101927825	XR_007062569.1	n.557+577C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAVIN3	ENST00000303927.4	c.203G>C	p.Ser68Thr	missense_variant	1/2	1	NM_145040.3	P1
	ENST00000655261.1	n.61+577C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00271 AC: 413 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00938

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000597 AC: 101 AN: 169206 Hom.: 1 AF XY: 0.000552 AC XY: 52 AN XY: 94208

Gnomad AFR exome AF: 0.00968

Gnomad AMR exome AF: 0.000280

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000782

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000140

Gnomad OTH exome AF: 0.000645

GnomAD4 exome AF: 0.000280 AC: 396 AN: 1413526 Hom.: 1 Cov.: 33 AF XY: 0.000245 AC XY: 172 AN XY: 700960

Gnomad4 AFR exome AF: 0.0102

Gnomad4 AMR exome AF: 0.000200

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000365

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000548

Gnomad4 OTH exome AF: 0.000747

GnomAD4 genome AF: 0.00271 AC: 413 AN: 152346 Hom.: 0 Cov.: 33 AF XY: 0.00246 AC XY: 183 AN XY: 74498

Gnomad4 AFR AF: 0.00938

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000557 Hom.: 1

Bravo AF: 0.00318

ESP6500AA AF: 0.00707 AC: 30

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000523 AC: 61

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.33
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.079	T;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.68	T;T
MetaRNN	Benign	0.0081	T;T
MetaSVM	Benign	-0.71	T
MutationTaster	Benign	0.91	D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.091
Sift	Benign	0.17	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.93	P;.
Vest4		0.068
MVP		0.55
MPC		1.1
ClinPred		0.036	T
GERP RS		4.9
Varity_R		0.28
gMVP		0.28

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: rs11544766; hg19: chr11-6341504;