dbSNP rs10113: CALM3:c.*238T>C (chr19-46609391-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.389

Variant links:

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]

CALM3 links:

ENSG00000269292 (HGNC:):

ENSG00000269292 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
CALM3	NM_005184.4 link	c.*238T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000291295.14	NP_005175.2	P0DP23P0DP24P0DP25B4DJ51Q9BRL5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALM3	ENST00000291295.14 link	c.*238T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_005184.4	ENSP00000291295.8		P0DP25

Frequencies

GnomAD3 genomes

AF:

0.499

AC:

75752

AN:

151664

Hom.:

18940

Cov.:

show subpopulations

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.:

AF XY:

0.487

AC XY:

111674

AN XY:

229402

show subpopulations

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.:

AF XY:

0.498

AC XY:

36897

AN XY:

74152

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over