rs907105022

Variant names:

• chr11-6320290-C-G
• rs907105022
• NM_145040.3:c.187G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-6320290-C-G
• chr11-6320290-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_145040.3(CAVIN3):​c.187G>C​(p.Gly63Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000447 in 1,566,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: CAVIN3 NM_145040.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.95
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18304846).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

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.187G>C	p.Gly63Arg	missense	Exon 1 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.187G>C	p.Gly63Arg	missense	Exon 1 of 2	ENSP00000307292.3	Q969G5
	CAVIN3	ENST00000530979.1	TSL:2	c.187G>C	p.Gly63Arg	missense	Exon 1 of 3	ENSP00000432047.1	E9PIE3
	CAVIN3	ENST00000954671.1		c.187G>C	p.Gly63Arg	missense	Exon 1 of 3	ENSP00000624730.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152198 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000118 AC: 2 AN: 169560 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000149

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000424 AC: 6 AN: 1414252 Hom.: 0 Cov.: 33 AF XY: 0.00000285 AC XY: 2 AN XY: 701440

African (AFR) AF: 0.00 AC: 0 AN: 32478

American (AMR) AF: 0.00 AC: 0 AN: 40038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25492

East Asian (EAS) AF: 0.0000801 AC: 3 AN: 37476

South Asian (SAS) AF: 0.00 AC: 0 AN: 82220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095714

Other (OTH) AF: 0.0000339 AC: 2 AN: 58942

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152198 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions as Germline

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	Uncertain	0.41
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.67	T
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.99	T
PhyloP100		2.0
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.16
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.016	D
Polyphen		0.039	B
Vest4		0.21
MutPred		0.28		Gain of MoRF binding (P = 0.0577)
MVP		0.41
MPC		0.44
ClinPred		0.31	T
GERP RS		0.97
PromoterAI		-0.071	Neutral
Varity_R		0.20
gMVP		0.20
Mutation Taster		=84/16	polymorphism

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: rs907105022; hg19: chr11-6341520;