chr11-6319528-C-A

Variant names:

• chr11-6319528-C-A
• rs1184529596
• NM_145040.3:c.421G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145040.3(CAVIN3):​c.421G>T​(p.Ala141Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000314 in 1,593,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CAVIN3 NM_145040.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.00
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048496097).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN3	NM_145040.3	MANE Select	c.421G>T	p.Ala141Ser	missense	Exon 2 of 2	NP_659477.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN3	ENST00000303927.4	TSL:1 MANE Select	c.421G>T	p.Ala141Ser	missense	Exon 2 of 2	ENSP00000307292.3	Q969G5
	CAVIN3	ENST00000530979.1	TSL:2	c.517G>T	p.Ala173Ser	missense	Exon 3 of 3	ENSP00000432047.1	E9PIE3
	CAVIN3	ENST00000954671.1		c.436G>T	p.Ala146Ser	missense	Exon 3 of 3	ENSP00000624730.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152258 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441606 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 716752

African (AFR) AF: 0.0000301 AC: 1 AN: 33190

American (AMR) AF: 0.00 AC: 0 AN: 43364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25522

East Asian (EAS) AF: 0.00 AC: 0 AN: 39290

South Asian (SAS) AF: 0.00 AC: 0 AN: 84340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43698

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106690

Other (OTH) AF: 0.00 AC: 0 AN: 59778

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152258 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74388

African (AFR) AF: 0.0000965 AC: 4 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.88
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.0
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.055
Sift	Benign	0.50	T
Sift4G	Benign	0.36	T
Polyphen		0.28	B
Vest4		0.11
MutPred		0.23		Gain of phosphorylation at A141 (P = 0.0241)
MVP		0.38
MPC		0.36
ClinPred		0.26	T
GERP RS		4.9
Varity_R		0.12
gMVP		0.063
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1184529596; hg19: chr11-6340758;