19-46609483-C-T

Position:

• chr19-46609483-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALM3	NM_005184.4	c.*330C>T		3_prime_UTR_variant	6/6	ENST00000291295.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALM3	ENST00000291295.14	c.*330C>T		3_prime_UTR_variant	6/6	1	NM_005184.4	P1
	ENST00000597609.1	n.195-105G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.369

Gnomad4 AMR exome AF: 0.469

Gnomad4 ASJ exome AF: 0.385

Gnomad4 EAS exome AF: 0.492

Gnomad4 SAS exome AF: 0.383

Gnomad4 FIN exome AF: 0.328

Gnomad4 NFE exome AF: 0.351

Gnomad4 OTH exome AF: 0.376

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

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.366

Alfa AF: 0.362 Hom.: 9522

Bravo AF: 0.382

Asia WGS AF: 0.439 AC: 1524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.83

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: rs710889; hg19: chr19-47112740;