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

Variant summary

Our verdict is . 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: G2P, ClinGen

CALM3 links:

ENSG00000269292 (HGNC:):

ENSG00000269292 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_005184.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005184.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CALM3	NM_005184.4	MANE Select	c.*330C>T	3_prime_UTR	Exon 6 of 6	NP_005175.2	P0DP25
CALM3	NM_001329922.1		c.*330C>T	3_prime_UTR	Exon 6 of 6	NP_001316851.1	P0DP23
CALM3	NM_001329921.1		c.*330C>T	3_prime_UTR	Exon 6 of 6	NP_001316850.1	Q96HY3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CALM3	ENST00000291295.14	TSL:1 MANE Select	c.*330C>T	3_prime_UTR	Exon 6 of 6	ENSP00000291295.8	P0DP25
CALM3	ENST00000599839.5	TSL:1	c.*330C>T	3_prime_UTR	Exon 7 of 7	ENSP00000471225.1	Q96HY3
CALM3	ENST00000866718.1		c.*330C>T	3_prime_UTR	Exon 6 of 6	ENSP00000536777.1

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over