11-6319501-G-A

Variant names:

• chr11-6319501-G-A
• rs747325306
• NM_145040.3:c.448C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BS2

The NM_145040.3(CAVIN3):​c.448C>T​(p.Gln150*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,448,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: CAVIN3 NM_145040.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08
• Publications: 1 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
• BS2: High AC in GnomAdExome4 at 5 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.448C>T	p.Gln150*	stop_gained	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.448C>T	p.Gln150*	stop_gained	Exon 2 of 2	ENSP00000307292.3	Q969G5
	CAVIN3	ENST00000530979.1	TSL:2	c.544C>T	p.Gln182*	stop_gained	Exon 3 of 3	ENSP00000432047.1	E9PIE3
	CAVIN3	ENST00000954671.1		c.463C>T	p.Gln155*	stop_gained	Exon 3 of 3	ENSP00000624730.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000889 AC: 2 AN: 225024 AF XY: 0.00000807

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000197

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1448188 Hom.: 0 Cov.: 36 AF XY: 0.00000416 AC XY: 3 AN XY: 720304

African (AFR) AF: 0.00 AC: 0 AN: 33280

American (AMR) AF: 0.00 AC: 0 AN: 43888

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25636

East Asian (EAS) AF: 0.00 AC: 0 AN: 39614

South Asian (SAS) AF: 0.00 AC: 0 AN: 84942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000451 AC: 5 AN: 1108860

Other (OTH) AF: 0.00 AC: 0 AN: 59932

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	39
DANN	Uncertain	1.0
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.024
FATHMM_MKL	Benign	0.030	N
PhyloP100		2.1
Vest4		0.85
GERP RS		2.8
Mutation Taster		=50/150	disease causing

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: rs747325306; hg19: chr11-6340731; COSMIC: COSV58268893; COSMIC: COSV58268893;