19-46601449-T-TG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_005184.4(CALM3):c.3+18dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000455 in 1,495,402 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000048 (1 hom.)
• Consequence: CALM3 NM_005184.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0850

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 19-46601449-T-TG is Benign according to our data. Variant chr19-46601449-T-TG is described in ClinVar as [Benign]. Clinvar id is 1618315.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALM3	NM_005184.4	c.3+18dup		intron_variant		ENST00000291295.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALM3	ENST00000291295.14	c.3+18dup		intron_variant		1	NM_005184.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151902 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000169 AC: 16 AN: 94458 Hom.: 1 AF XY: 0.000168 AC XY: 9 AN XY: 53472

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000528

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000679

Gnomad SAS exome AF: 0.000510

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000315

Gnomad OTH exome AF: 0.000357

GnomAD4 exome AF: 0.0000476 AC: 64 AN: 1343382 Hom.: 1 Cov.: 30 AF XY: 0.0000588 AC XY: 39 AN XY: 662970

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000324

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000132

Gnomad4 SAS exome AF: 0.000498

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000152

Gnomad4 OTH exome AF: 0.0000903

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152020 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74326

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000340

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Long QT syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 28, 2023

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Computational scores

Source: dbNSFP v4.3

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: rs761428143; hg19: chr19-47104706;