19-46601278-T-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000597743.5(CALM3):c.-157T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 544,608 control chromosomes in the GnomAD database, including 11,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2483 hom., cov: 32)
  • Exomes 𝑓: 0.20 (8663 hom.)
• Consequence: CALM3 ENST00000597743.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.301

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 19-46601278-T-A is Benign according to our data. Variant chr19-46601278-T-A is described in ClinVar as [Benign]. Clinvar id is 1167461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALM3	NM_001329921.1	c.-106+102T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALM3	ENST00000597743.5	c.-157T>A		5_prime_UTR_variant	1/5	4
CALM3	ENST00000391918.6	c.-106+102T>A		intron_variant		2
CALM3	ENST00000477244.5			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 23885 AN: 148300 Hom.: 2484 Cov.: 32

Gnomad AFR AF: 0.0709

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.0487

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.198 AC: 78428 AN: 396200 Hom.: 8663 Cov.: 7 AF XY: 0.199 AC XY: 39581 AN XY: 198484

Gnomad4 AFR exome AF: 0.0593

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.0901

Gnomad4 EAS exome AF: 0.329

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.331

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.161 AC: 23882 AN: 148408 Hom.: 2483 Cov.: 32 AF XY: 0.165 AC XY: 11974 AN XY: 72438

Gnomad4 AFR AF: 0.0708

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0911

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.138

Alfa AF: 0.163 Hom.: 282

Bravo AF: 0.144

Asia WGS AF: 0.245 AC: 825 AN: 3374

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Long QT syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is associated with the following publications: (PMID: 19429631) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	18
Dann	Benign	0.93

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

LitVar

Other links and lift over

dbSNP: rs150954567; hg19: chr19-47104535; COSMIC: COSV52194442; COSMIC: COSV52194442;