Genetic Variant CALM3:c.*728A>G (chr19-46609881-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005184.4(CALM3):c.*728A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 152,844 control chromosomes in the GnomAD database, including 64,862 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 0.92 ( 64572 hom., cov: 31)

Exomes 𝑓: 0.91 ( 290 hom. )

Consequence

CALM3
NM_005184.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.618

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALM3	NM_005184.4 link	c.*728A>G		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.*728A>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_005184.4	ENSP00000291295.8		P0DP25

Frequencies

GnomAD3 genomes

AF:

0.921

AC:

139986

AN:

152026

Hom.:

64513

Cov.:

show subpopulations

Gnomad AFR

AF:

0.957

Gnomad AMI

AF:

0.879

Gnomad AMR

AF:

0.934

Gnomad ASJ

AF:

0.934

Gnomad EAS

AF:

0.974

Gnomad SAS

AF:

0.960

Gnomad FIN

AF:

0.900

Gnomad MID

AF:

0.921

Gnomad NFE

AF:

0.892

Gnomad OTH

AF:

0.913

GnomAD4 exome

AF:

0.914

AC:

640

AN:

700

Hom.:

290

Cov.:

AF XY:

0.931

AC XY:

432

AN XY:

464

show subpopulations

Gnomad4 AFR exome

AF:

0.833

Gnomad4 AMR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.955

Gnomad4 FIN exome

AF:

0.907

Gnomad4 NFE exome

AF:

0.921

Gnomad4 OTH exome

AF:

0.929

GnomAD4 genome

AF:

0.921

AC:

140104

AN:

152144

Hom.:

64572

Cov.:

AF XY:

0.923

AC XY:

68623

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.957

Gnomad4 AMR

AF:

0.934

Gnomad4 ASJ

AF:

0.934

Gnomad4 EAS

AF:

0.974

Gnomad4 SAS

AF:

0.960

Gnomad4 FIN

AF:

0.900

Gnomad4 NFE

AF:

0.892

Gnomad4 OTH

AF:

0.914

Alfa

AF:

0.901

Hom.:

56917

Bravo

AF:

0.925

Asia WGS

AF:

0.977

AC:

3396

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

2.9

DANN

Benign

0.78

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over