NM_033337.3:c.*645A>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033337.3(CAV3):c.*645A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,820 control chromosomes in the GnomAD database, including 13,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13442 hom., cov: 30)

Exomes 𝑓: 0.36 ( 5 hom. )

Consequence

CAV3
NM_033337.3 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: -0.110

Publications

9 publications found

Variant links:

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]

CAV3 links:

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]

OXTR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 3-8746512-A-T is Benign according to our data. Variant chr3-8746512-A-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 31706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CAV3	NM_033337.3 link	c.*645A>T	3_prime_UTR_variant	Exon 2 of 2	ENST00000343849.3	NP_203123.1	P56539
CAV3	NM_001234.5 link	c.*549A>T	3_prime_UTR_variant	Exon 3 of 3		NP_001225.1	P56539
OXTR	XR_007095681.1 link	n.1885-3910T>A	intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CAV3	ENST00000343849.3 link	c.*645A>T	3_prime_UTR_variant	Exon 2 of 2	1	NM_033337.3	ENSP00000341940.2	P56539
CAV3	ENST00000397368.2 link	c.*549A>T	3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000380525.2	P56539
CAV3	ENST00000472766.1 link	n.155+12522A>T	intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.416

AC:

63064

AN:

151636

Hom.:

13436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.385

Gnomad AMI

AF:

0.307

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.422

Gnomad EAS

AF:

0.313

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.546

Gnomad MID

AF:

0.366

Gnomad NFE

AF:

0.432

Gnomad OTH

AF:

0.396

GnomAD4 exome

AF:

0.364

AC:

AN:

Hom.:

Cov.:

AF XY:

0.325

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.333

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.391

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.416

AC:

63115

AN:

151754

Hom.:

13442

Cov.:

AF XY:

0.416

AC XY:

30844

AN XY:

74124

show subpopulations

African (AFR)

AF:

0.385

AC:

15929

AN:

41342

American (AMR)

AF:

0.442

AC:

6750

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.422

AC:

1460

AN:

3460

East Asian (EAS)

AF:

0.312

AC:

1605

AN:

5138

South Asian (SAS)

AF:

0.223

AC:

1072

AN:

4812

European-Finnish (FIN)

AF:

0.546

AC:

5746

AN:

10520

Middle Eastern (MID)

AF:

0.366

AC:

107

AN:

292

European-Non Finnish (NFE)

AF:

0.432

AC:

29328

AN:

67914

Other (OTH)

AF:

0.398

AC:

840

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1838

3676

5515

7353

9191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

582

1164

1746

2328

2910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.435

Hom.:

1949

Bravo

AF:

0.412

Asia WGS

AF:

0.281

AC:

978

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Apr 15, 2012

Leiden Muscular Dystrophy (CAV3)

Significance:not provided

Review Status:no classification provided

Collection Method:curation

- -

May 10, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Limb-Girdle Muscular Dystrophy, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Caveolinopathy

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Congenital long QT syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.3

(source)

DANN

Benign

0.57

PhyloP100

-0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over