rs10113

Variant names:

• chr19-46609391-T-C
• rs10113
• NM_005184.4:c.*238T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005184.4(CALM3):​c.*238T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 588,516 control chromosomes in the GnomAD database, including 72,121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (18941 hom., cov: 30)
  • Exomes 𝑓: 0.49 (53180 hom.)
• Consequence: CALM3 NM_005184.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.389
• 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• catecholaminergic polymorphic ventricular tachycardia

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen, G2P

ENSG00000269292 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-46609391-T-C is Benign according to our data. Variant chr19-46609391-T-C is described in ClinVar as Benign. ClinVar VariationId is 1175610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.529 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.*238T>C		3_prime_UTR	Exon 6 of 6	NP_005175.2
	CALM3	NM_001329922.1		c.*238T>C		3_prime_UTR	Exon 6 of 6	NP_001316851.1
	CALM3	NM_001329921.1		c.*238T>C		3_prime_UTR	Exon 6 of 6	NP_001316850.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALM3	ENST00000291295.14	TSL:1 MANE Select	c.*238T>C		3_prime_UTR	Exon 6 of 6	ENSP00000291295.8
	CALM3	ENST00000599839.5	TSL:1	c.*238T>C		3_prime_UTR	Exon 7 of 7	ENSP00000471225.1
	CALM3	ENST00000866718.1		c.*238T>C		3_prime_UTR	Exon 6 of 6	ENSP00000536777.1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75752 AN: 151664 Hom.: 18940 Cov.: 30

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.481

GnomAD4 exome AF: 0.490 AC: 213852 AN: 436734 Hom.: 53180 Cov.: 3 AF XY: 0.487 AC XY: 111674 AN XY: 229402

African (AFR) AF: 0.534 AC: 6539 AN: 12248

American (AMR) AF: 0.577 AC: 10787 AN: 18690

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 6939 AN: 13600

East Asian (EAS) AF: 0.549 AC: 16453 AN: 29968

South Asian (SAS) AF: 0.440 AC: 18549 AN: 42172

European-Finnish (FIN) AF: 0.464 AC: 13608 AN: 29322

Middle Eastern (MID) AF: 0.527 AC: 1869 AN: 3548

European-Non Finnish (NFE) AF: 0.484 AC: 126551 AN: 261680

Other (OTH) AF: 0.492 AC: 12557 AN: 25506

GnomAD4 genome AF: 0.499 AC: 75801 AN: 151782 Hom.: 18941 Cov.: 30 AF XY: 0.498 AC XY: 36897 AN XY: 74152

African (AFR) AF: 0.524 AC: 21679 AN: 41360

American (AMR) AF: 0.539 AC: 8215 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1737 AN: 3472

East Asian (EAS) AF: 0.497 AC: 2535 AN: 5102

South Asian (SAS) AF: 0.451 AC: 2171 AN: 4810

European-Finnish (FIN) AF: 0.462 AC: 4872 AN: 10542

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 32993 AN: 67938

Other (OTH) AF: 0.481 AC: 1014 AN: 2110

Alfa AF: 0.491 Hom.: 40054

Bravo AF: 0.509

Asia WGS AF: 0.483 AC: 1679 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.9
DANN	Benign	0.51
PhyloP100		0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs10113; hg19: chr19-47112648;