Variant rs13158477 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.4138A>G(p.Ile1380Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,613,318 control chromosomes in the GnomAD database, including 19,313 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.14 ( 1653 hom., cov: 33)

Exomes 𝑓: 0.15 ( 17660 hom. )

Consequence

CMYA5
NM_153610.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.998

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=0.0015851259).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CMYA5	NM_153610.5 linkuse as main transcript	c.4138A>G	p.Ile1380Val	missense_variant	2/13	ENST00000446378.3	NP_705838.3
CMYA5	XM_047416911.1 linkuse as main transcript	c.4138A>G	p.Ile1380Val	missense_variant	2/6		XP_047272867.1
CMYA5	XR_001742036.3 linkuse as main transcript	n.4210A>G		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMYA5	ENST00000446378.3 linkuse as main transcript	c.4138A>G	p.Ile1380Val	missense_variant	2/13	5	NM_153610.5	ENSP00000394770	P1

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21879

AN:

152140

Hom.:

1654

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.223

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.0183

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.147

GnomAD3 exomes

AF:

0.137

AC:

34030

AN:

247868

Hom.:

2657

AF XY:

0.139

AC XY:

18629

AN XY:

134498

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.0113

Gnomad SAS exome

AF:

0.131

Gnomad FIN exome

AF:

0.191

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.150

GnomAD4 exome

AF:

0.152

AC:

222790

AN:

1461060

Hom.:

17660

Cov.:

AF XY:

0.152

AC XY:

110367

AN XY:

726802

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.110

Gnomad4 ASJ exome

AF:

0.152

Gnomad4 EAS exome

AF:

0.0245

Gnomad4 SAS exome

AF:

0.130

Gnomad4 FIN exome

AF:

0.190

Gnomad4 NFE exome

AF:

0.160

Gnomad4 OTH exome

AF:

0.150

GnomAD4 genome

AF:

0.144

AC:

21882

AN:

152258

Hom.:

1653

Cov.:

AF XY:

0.141

AC XY:

10526

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.124

Gnomad4 ASJ

AF:

0.154

Gnomad4 EAS

AF:

0.0181

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.196

Gnomad4 NFE

AF:

0.160

Gnomad4 OTH

AF:

0.145

Alfa

AF:

0.155

Hom.:

4771

Bravo

AF:

0.138

TwinsUK

AF:

0.149

AC:

553

ALSPAC

AF:

0.161

AC:

622

ESP6500AA

AF:

0.126

AC:

469

ESP6500EA

AF:

0.157

AC:

1285

ExAC

AF:

0.137

AC:

16597

Asia WGS

AF:

0.0870

AC:

305

AN:

3478

EpiCase

AF:

0.162

EpiControl

AF:

0.153

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.89

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.052

DANN

Benign

0.13

DEOGEN2

Benign

0.016

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.34

MutationTaster

Benign

1.0

PrimateAI

Benign

0.21

PROVEAN

Benign

0.53

REVEL

Benign

0.054

Sift

Benign

0.69

Sift4G

Benign

0.57

Polyphen

0.0010

Vest4

0.0010

MPC

0.048

ClinPred

0.0028

GERP RS

-0.88

Varity_R

0.025

gMVP

0.064

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