19-46601278-T-C

Variant names:

• chr19-46601278-T-C
• rs150954567
• ENST00000866714.1:c.-157T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001329921.1(CALM3):​c.-106+102T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000755 in 397,090 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: CALM3 NM_001329921.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• Publications: 0 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

ENSG00000291145 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329921.1. 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_001329921.1		c.-106+102T>C		intron	N/A	NP_001316850.1	Q96HY3
	CALM3	NM_005184.4	MANE Select	c.-157T>C		upstream_gene	N/A	NP_005175.2	P0DP25
	CALM3	NM_001329924.2		c.-263T>C		upstream_gene	N/A	NP_001316853.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALM3	ENST00000866714.1		c.-157T>C		5_prime_UTR	Exon 1 of 6	ENSP00000536773.1
	CALM3	ENST00000866717.1		c.-62T>C		5_prime_UTR	Exon 1 of 7	ENSP00000536776.1
	CALM3	ENST00000866716.1		c.-157T>C		5_prime_UTR	Exon 1 of 6	ENSP00000536775.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000755 AC: 3 AN: 397090 Hom.: 0 Cov.: 7 AF XY: 0.0000101 AC XY: 2 AN XY: 198888

African (AFR) AF: 0.00 AC: 0 AN: 7612

American (AMR) AF: 0.00 AC: 0 AN: 2930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4928

East Asian (EAS) AF: 0.00 AC: 0 AN: 10160

South Asian (SAS) AF: 0.00 AC: 0 AN: 12958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9840

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1130

European-Non Finnish (NFE) AF: 0.00000904 AC: 3 AN: 331808

Other (OTH) AF: 0.00 AC: 0 AN: 15724

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Benign	0.77
PhyloP100		0.30
PromoterAI		-0.098	Neutral

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: rs150954567; hg19: chr19-47104535;