Genetic Variant CALM3:c.*330C>T (chr19-46609483-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005184.4(CALM3):c.*330C>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 0.371 in 395,252 control chromosomes in the GnomAD database, including 28,107 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 10684 hom., cov: 29)

Exomes 𝑓: 0.37 ( 17423 hom. )

Consequence

CALM3
NM_005184.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36

Publications

20 publications found

Variant links:

Genes affected

CALM3 (HGNC:1449): (calmodulin 3) This gene encodes a member of a family of proteins that binds calcium and functions as a enzymatic co-factor. Activity of this protein is important in the regulation of the cell cycle and cytokinesis. Multiple alternatively spliced transcript variants have been observed at this gene. [provided by RefSeq, Aug 2016]

CALM3 Gene-Disease associations (from GenCC):

familial long QT syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
long QT syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
long QT syndrome 16
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
catecholaminergic polymorphic ventricular tachycardia
Inheritance: AD Classification: MODERATE Submitted by: ClinGen, G2P

CALM3 links:

ENSG00000269292 (HGNC:):

ENSG00000269292 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALM3	NM_005184.4 link	c.*330C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000291295.14	NP_005175.2	P0DP23P0DP24P0DP25B4DJ51Q9BRL5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALM3	ENST00000291295.14 link	c.*330C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_005184.4	ENSP00000291295.8		P0DP25

Frequencies

GnomAD3 genomes

AF:

0.373

AC:

56536

AN:

151436

Hom.:

10679

Cov.:

show subpopulations

Gnomad AFR

AF:

0.371

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.365

GnomAD4 exome

AF:

0.369

AC:

89901

AN:

243698

Hom.:

17423

Cov.:

AF XY:

0.371

AC XY:

46892

AN XY:

126496

show subpopulations

African (AFR)

AF:

0.369

AC:

2710

AN:

7354

American (AMR)

AF:

0.469

AC:

3551

AN:

7578

Ashkenazi Jewish (ASJ)

AF:

0.385

AC:

3259

AN:

8468

East Asian (EAS)

AF:

0.492

AC:

8095

AN:

16462

South Asian (SAS)

AF:

0.383

AC:

7187

AN:

18780

European-Finnish (FIN)

AF:

0.328

AC:

5287

AN:

16128

Middle Eastern (MID)

AF:

0.383

AC:

1061

AN:

2768

European-Non Finnish (NFE)

AF:

0.351

AC:

53066

AN:

151028

Other (OTH)

AF:

0.376

AC:

5685

AN:

15132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

2636

5273

7909

10546

13182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

304

608

912

1216

1520

<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:

0.373

AC:

56579

AN:

151554

Hom.:

10684

Cov.:

AF XY:

0.375

AC XY:

27762

AN XY:

73980

show subpopulations

African (AFR)

AF:

0.371

AC:

15308

AN:

41314

American (AMR)

AF:

0.444

AC:

6758

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

1361

AN:

3470

East Asian (EAS)

AF:

0.458

AC:

2326

AN:

5074

South Asian (SAS)

AF:

0.411

AC:

1976

AN:

4804

European-Finnish (FIN)

AF:

0.337

AC:

3532

AN:

10496

Middle Eastern (MID)

AF:

0.394

AC:

115

AN:

292

European-Non Finnish (NFE)

AF:

0.356

AC:

24138

AN:

67876

Other (OTH)

AF:

0.366

AC:

768

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1761

3523

5284

7046

8807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.366

Hom.:

14012

Bravo

AF:

0.382

Asia WGS

AF:

0.439

AC:

1524

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

1.4

Mutation Taster

=99/1

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

Computational scores

Splicing

Publications

Other links and lift over