19-46609483-C-T

Variant names:

• chr19-46609483-C-T
• rs710889
• NM_005184.4:c.*330C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 20 publications found

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

ENSG00000269292 (HGNC:):

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 29

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.: 0 AF XY: 0.371 AC XY: 46892 AN XY: 126496

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

GnomAD4 genome AF: 0.373 AC: 56579 AN: 151554 Hom.: 10684 Cov.: 29 AF XY: 0.375 AC XY: 27762 AN XY: 73980

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

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	14
DANN	Benign	0.83
PhyloP100		1.4
Mutation Taster		=99/1	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: rs710889; hg19: chr19-47112740;