Variant 5-79737568-G-A 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.8803G>A(p.Gly2935Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0341 in 1,613,564 control chromosomes in the GnomAD database, including 1,453 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.037 ( 149 hom., cov: 32)

Exomes 𝑓: 0.034 ( 1304 hom. )

Consequence

CMYA5
NM_153610.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.89

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:

CMYA5 (HGNC:):

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=0.0013951659).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMYA5	NM_153610.5 linkuse as main transcript	c.8803G>A	p.Gly2935Arg	missense_variant	2/13	ENST00000446378.3	NP_705838.3	Q8N3K9
CMYA5	XM_047416911.1 linkuse as main transcript	c.8803G>A	p.Gly2935Arg	missense_variant	2/6		XP_047272867.1
CMYA5	XR_001742036.3 linkuse as main transcript	n.8875G>A		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.8803G>A	p.Gly2935Arg	missense_variant	2/13	5	NM_153610.5	ENSP00000394770.2		Q8N3K9

Frequencies

GnomAD3 genomes

AF:

0.0368

AC:

5592

AN:

152162

Hom.:

150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0424

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0227

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.0998

Gnomad SAS

AF:

0.0796

Gnomad FIN

AF:

0.00867

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0277

Gnomad OTH

AF:

0.0377

GnomAD3 exomes

AF:

0.0414

AC:

10239

AN:

247426

Hom.:

376

AF XY:

0.0442

AC XY:

5941

AN XY:

134270

show subpopulations

Gnomad AFR exome

AF:

0.0439

Gnomad AMR exome

AF:

0.0196

Gnomad ASJ exome

AF:

0.140

Gnomad EAS exome

AF:

0.0907

Gnomad SAS exome

AF:

0.0751

Gnomad FIN exome

AF:

0.00707

Gnomad NFE exome

AF:

0.0281

Gnomad OTH exome

AF:

0.0458

GnomAD4 exome

AF:

0.0338

AC:

49442

AN:

1461284

Hom.:

1304

Cov.:

AF XY:

0.0358

AC XY:

26002

AN XY:

726874

show subpopulations

Gnomad4 AFR exome

AF:

0.0440

Gnomad4 AMR exome

AF:

0.0203

Gnomad4 ASJ exome

AF:

0.138

Gnomad4 EAS exome

AF:

0.0908

Gnomad4 SAS exome

AF:

0.0780

Gnomad4 FIN exome

AF:

0.00859

Gnomad4 NFE exome

AF:

0.0265

Gnomad4 OTH exome

AF:

0.0462

GnomAD4 genome

AF:

0.0368

AC:

5598

AN:

152280

Hom.:

149

Cov.:

AF XY:

0.0374

AC XY:

2786

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0423

Gnomad4 AMR

AF:

0.0226

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.0997

Gnomad4 SAS

AF:

0.0798

Gnomad4 FIN

AF:

0.00867

Gnomad4 NFE

AF:

0.0277

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0360

Hom.:

327

Bravo

AF:

0.0370

TwinsUK

AF:

0.0264

AC:

ALSPAC

AF:

0.0309

AC:

119

ESP6500AA

AF:

0.0402

AC:

149

ESP6500EA

AF:

0.0347

AC:

284

ExAC

AF:

0.0409

AC:

4936

Asia WGS

AF:

0.100

AC:

347

AN:

3478

EpiCase

AF:

0.0328

EpiControl

AF:

0.0352

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.52

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.063

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-4.8

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.018

Polyphen

0.99

Vest4

0.094

MutPred

0.17

Gain of solvent accessibility (P = 0.019);

MPC

0.38

ClinPred

0.044

GERP RS

5.1

Varity_R

0.64

gMVP

0.36

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