19-46601522-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005184.4(CALM3):c.3+85A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0241 in 1,251,930 control chromosomes in the GnomAD database, including 530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (42 hom., cov: 32)
  • Exomes 𝑓: 0.025 (488 hom.)
• Consequence: CALM3 NM_005184.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.63

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-46601522-A-C is Benign according to our data. Variant chr19-46601522-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1207851.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALM3	NM_005184.4	c.3+85A>C		intron_variant		ENST00000291295.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALM3	ENST00000291295.14	c.3+85A>C		intron_variant		1	NM_005184.4	P1

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2655 AN: 152128 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.00364

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0854

Gnomad FIN AF: 0.00943

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0251

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.0250 AC: 27472 AN: 1099688 Hom.: 488 AF XY: 0.0260 AC XY: 13864 AN XY: 533008

Gnomad4 AFR exome AF: 0.00357

Gnomad4 AMR exome AF: 0.0107

Gnomad4 ASJ exome AF: 0.0229

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.0777

Gnomad4 FIN exome AF: 0.00978

Gnomad4 NFE exome AF: 0.0242

Gnomad4 OTH exome AF: 0.0249

GnomAD4 genome AF: 0.0174 AC: 2653 AN: 152242 Hom.: 42 Cov.: 32 AF XY: 0.0175 AC XY: 1304 AN XY: 74462

Gnomad4 AFR AF: 0.00363

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.0210

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0853

Gnomad4 FIN AF: 0.00943

Gnomad4 NFE AF: 0.0251

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0179 Hom.: 3

Bravo AF: 0.0148

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.23
Dann	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs184847124; hg19: chr19-47104779;