rs13087941

Variant names:

• chr3-8745534-T-C
• rs13087941
• NM_033337.3:c.123T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_033337.3(CAV3):​c.123T>C​(p.Phe41Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,612,768 control chromosomes in the GnomAD database, including 43,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4286 hom., cov: 32)
  • Exomes 𝑓: 0.22 (39429 hom.)
• Consequence: CAV3 NM_033337.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:16 O:1
• Conservation: PhyloP100: -0.510
• Publications: 19 publications found

Genes affected

CAV3 (HGNC:1529): (caveolin 3) This gene encodes a caveolin family member, which functions as a component of the caveolae plasma membranes found in most cell types. Caveolin proteins are proposed to be scaffolding proteins for organizing and concentrating certain caveolin-interacting molecules. Mutations identified in this gene lead to interference with protein oligomerization or intra-cellular routing, disrupting caveolae formation and resulting in Limb-Girdle muscular dystrophy type-1C (LGMD-1C), hyperCKemia or rippling muscle disease (RMD). Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites and contain two potential translation initiation sites. [provided by RefSeq, Jul 2008]

OXTR (HGNC:8529): (oxytocin receptor) The protein encoded by this gene belongs to the G-protein coupled receptor family and acts as a receptor for oxytocin. Its activity is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. The oxytocin-oxytocin receptor system plays an important role in the uterus during parturition. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-8745534-T-C is Benign according to our data. Variant chr3-8745534-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 31717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033337.3. 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
	CAV3	NM_033337.3	MANE Select	c.123T>C	p.Phe41Phe	synonymous	Exon 2 of 2	NP_203123.1	P56539
	CAV3	NM_001234.5		c.123T>C	p.Phe41Phe	synonymous	Exon 2 of 3	NP_001225.1	P56539

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV3	ENST00000343849.3	TSL:1 MANE Select	c.123T>C	p.Phe41Phe	synonymous	Exon 2 of 2	ENSP00000341940.2	P56539
	CAV3	ENST00000397368.2	TSL:1	c.123T>C	p.Phe41Phe	synonymous	Exon 2 of 3	ENSP00000380525.2	P56539
	CAV3	ENST00000472766.1	TSL:2	n.155+11544T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34733 AN: 152002 Hom.: 4283 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.0627

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.196

GnomAD2 exomes AF: 0.182 AC: 45650 AN: 250760 AF XY: 0.178

Gnomad AFR exome AF: 0.291

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.150

Gnomad EAS exome AF: 0.00658

Gnomad FIN exome AF: 0.261

Gnomad NFE exome AF: 0.239

Gnomad OTH exome AF: 0.177

GnomAD4 exome AF: 0.222 AC: 323714 AN: 1460648 Hom.: 39429 Cov.: 33 AF XY: 0.217 AC XY: 157360 AN XY: 726664

African (AFR) AF: 0.294 AC: 9840 AN: 33444

American (AMR) AF: 0.107 AC: 4786 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 4028 AN: 26132

East Asian (EAS) AF: 0.00348 AC: 138 AN: 39698

South Asian (SAS) AF: 0.0695 AC: 5992 AN: 86214

European-Finnish (FIN) AF: 0.264 AC: 14089 AN: 53364

Middle Eastern (MID) AF: 0.104 AC: 596 AN: 5758

European-Non Finnish (NFE) AF: 0.245 AC: 272019 AN: 1110950

Other (OTH) AF: 0.203 AC: 12226 AN: 60368

GnomAD4 genome AF: 0.229 AC: 34765 AN: 152120 Hom.: 4286 Cov.: 32 AF XY: 0.222 AC XY: 16541 AN XY: 74366

African (AFR) AF: 0.286 AC: 11856 AN: 41488

American (AMR) AF: 0.162 AC: 2482 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 521 AN: 3472

East Asian (EAS) AF: 0.0104 AC: 54 AN: 5172

South Asian (SAS) AF: 0.0629 AC: 303 AN: 4816

European-Finnish (FIN) AF: 0.257 AC: 2719 AN: 10572

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16229 AN: 67988

Other (OTH) AF: 0.197 AC: 416 AN: 2116

Alfa AF: 0.227 Hom.: 6767

Bravo AF: 0.226

Asia WGS AF: 0.0680 AC: 238 AN: 3478

EpiCase AF: 0.222

EpiControl AF: 0.221

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	9	not specified (9)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Caveolinopathy (1)
-	-	1	Congenital long QT syndrome (1)
-	-	1	Limb-Girdle Muscular Dystrophy, Dominant (1)
-	-	1	Long QT syndrome (1)
-	-	1	not provided (2)
-	-	1	Rippling muscle disease 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.21
DANN	Benign	0.49
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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: rs13087941; hg19: chr3-8787220; COSMIC: COSV57480079; COSMIC: COSV57480079;