Genetic Variant NM_005184.4:c.3+14G>C (chr19-46601451-G-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005184.4(CALM3):c.3+14G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000521 in 1,343,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000052 ( 0 hom. )

Consequence

CALM3
NM_005184.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0990

Publications

0 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
catecholaminergic polymorphic ventricular tachycardia
Inheritance: AD Classification: MODERATE Submitted by: G2P, ClinGen

CALM3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 19-46601451-G-C is Benign according to our data. Variant chr19-46601451-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2195391.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 7 AD gene.

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.3+14G>C	intron	N/A	NP_005175.2	P0DP25
CALM3	NM_001329921.1		c.-106+275G>C	intron	N/A	NP_001316850.1	Q96HY3
CALM3	NM_001329924.2		c.-104+14G>C	intron	N/A	NP_001316853.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CALM3	ENST00000291295.14	TSL:1 MANE Select	c.3+14G>C	intron	N/A	ENSP00000291295.8	P0DP25
CALM3	ENST00000866718.1		c.3+14G>C	intron	N/A	ENSP00000536777.1
CALM3	ENST00000866714.1		c.3+14G>C	intron	N/A	ENSP00000536773.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000104

AC:

AN:

95732

AF XY:

0.00

show subpopulations

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:

0.0000311

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000521

AC:

AN:

1343082

Hom.:

Cov.:

AF XY:

0.00000453

AC XY:

AN XY:

662504

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27700

American (AMR)

AF:

0.00

AC:

AN:

31064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23672

East Asian (EAS)

AF:

0.00

AC:

AN:

30278

South Asian (SAS)

AF:

0.00

AC:

AN:

76208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38922

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5078

European-Non Finnish (NFE)

AF:

0.00000569

AC:

AN:

1054838

Other (OTH)

AF:

0.0000181

AC:

AN:

55322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Long QT syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.4

(source)

DANN

Benign

0.74

PhyloP100

-0.099

PromoterAI

0.0017

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over