rs10113

chr19-46609391-T-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.*238T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 588,516 control chromosomes in the GnomAD database, including 72,121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (18941 hom., cov: 30)
  • Exomes 𝑓: 0.49 (53180 hom.)
• Consequence: CALM3 NM_005184.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.389

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-46609391-T-C is Benign according to our data. Variant chr19-46609391-T-C is described in ClinVar as [Benign]. Clinvar id is 1175610.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALM3	NM_005184.4	c.*238T>C		3_prime_UTR_variant	6/6	ENST00000291295.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALM3	ENST00000291295.14	c.*238T>C		3_prime_UTR_variant	6/6	1	NM_005184.4	P1
	ENST00000597609.1	n.195-13A>G		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75752 AN: 151664 Hom.: 18940 Cov.: 30

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.481

GnomAD4 exome AF: 0.490 AC: 213852 AN: 436734 Hom.: 53180 Cov.: 3 AF XY: 0.487 AC XY: 111674 AN XY: 229402

Gnomad4 AFR exome AF: 0.534

Gnomad4 AMR exome AF: 0.577

Gnomad4 ASJ exome AF: 0.510

Gnomad4 EAS exome AF: 0.549

Gnomad4 SAS exome AF: 0.440

Gnomad4 FIN exome AF: 0.464

Gnomad4 NFE exome AF: 0.484

Gnomad4 OTH exome AF: 0.492

GnomAD4 genome AF: 0.499 AC: 75801 AN: 151782 Hom.: 18941 Cov.: 30 AF XY: 0.498 AC XY: 36897 AN XY: 74152

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.481

Alfa AF: 0.489 Hom.: 24768

Bravo AF: 0.509

Asia WGS AF: 0.483 AC: 1679 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	9.9
Dann	Benign	0.51
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: rs10113; hg19: chr19-47112648;