Variant rs16877135 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_153610.5(CMYA5):c.3998C>T(p.Ala1333Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0872 in 1,613,406 control chromosomes in the GnomAD database, including 10,823 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1859 hom., cov: 33)

Exomes 𝑓: 0.083 ( 8964 hom. )

Consequence

CMYA5
NM_153610.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.876

Variant links:

Genes affected

CMYA5 (HGNC:14305): (cardiomyopathy associated 5) Predicted to enable identical protein binding activity. Predicted to act upstream of or within negative regulation of calcineurin-NFAT signaling cascade; negative regulation of phosphoprotein phosphatase activity; and regulation of skeletal muscle adaptation. Located in cytosol; nuclear speck; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CMYA5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001995653).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CMYA5	NM_153610.5 linkuse as main transcript	c.3998C>T	p.Ala1333Val	missense_variant	2/13	ENST00000446378.3
CMYA5	XM_047416911.1 linkuse as main transcript	c.3998C>T	p.Ala1333Val	missense_variant	2/6
CMYA5	XR_001742036.3 linkuse as main transcript	n.4070C>T		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CMYA5	ENST00000446378.3 linkuse as main transcript	c.3998C>T	p.Ala1333Val	missense_variant	2/13	5	NM_153610.5	P1

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18813

AN:

152074

Hom.:

1843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0551

Gnomad ASJ

AF:

0.0568

Gnomad EAS

AF:

0.402

Gnomad SAS

AF:

0.0909

Gnomad FIN

AF:

0.0978

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0661

Gnomad OTH

AF:

0.0932

GnomAD3 exomes

AF:

0.103

AC:

25526

AN:

247654

Hom.:

2519

AF XY:

0.0986

AC XY:

13248

AN XY:

134314

show subpopulations

Gnomad AFR exome

AF:

0.232

Gnomad AMR exome

AF:

0.0357

Gnomad ASJ exome

AF:

0.0521

Gnomad EAS exome

AF:

0.408

Gnomad SAS exome

AF:

0.0945

Gnomad FIN exome

AF:

0.0989

Gnomad NFE exome

AF:

0.0664

Gnomad OTH exome

AF:

0.0761

GnomAD4 exome

AF:

0.0833

AC:

121770

AN:

1461214

Hom.:

8964

Cov.:

AF XY:

0.0828

AC XY:

60162

AN XY:

726876

show subpopulations

Gnomad4 AFR exome

AF:

0.240

Gnomad4 AMR exome

AF:

0.0382

Gnomad4 ASJ exome

AF:

0.0550

Gnomad4 EAS exome

AF:

0.465

Gnomad4 SAS exome

AF:

0.0928

Gnomad4 FIN exome

AF:

0.0985

Gnomad4 NFE exome

AF:

0.0658

Gnomad4 OTH exome

AF:

0.0910

GnomAD4 genome

AF:

0.124

AC:

18874

AN:

152192

Hom.:

1859

Cov.:

AF XY:

0.127

AC XY:

9445

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.231

Gnomad4 AMR

AF:

0.0549

Gnomad4 ASJ

AF:

0.0568

Gnomad4 EAS

AF:

0.403

Gnomad4 SAS

AF:

0.0910

Gnomad4 FIN

AF:

0.0978

Gnomad4 NFE

AF:

0.0660

Gnomad4 OTH

AF:

0.0922

Alfa

AF:

0.0807

Hom.:

1975

Bravo

AF:

0.127

TwinsUK

AF:

0.0693

AC:

257

ALSPAC

AF:

0.0654

AC:

252

ESP6500AA

AF:

0.224

AC:

845

ESP6500EA

AF:

0.0659

AC:

541

ExAC

AF:

0.107

AC:

12890

Asia WGS

AF:

0.237

AC:

825

AN:

3478

EpiCase

AF:

0.0609

EpiControl

AF:

0.0560

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

Cadd

Benign

2.1

Dann

Benign

0.97

DEOGEN2

Benign

0.020

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.20

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.66

REVEL

Benign

0.047

Sift

Benign

0.38

Sift4G

Benign

0.62

Polyphen

0.057

Vest4

0.016

MPC

0.055

ClinPred

0.0010

GERP RS

1.3

Varity_R

0.029

gMVP

0.18

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