Genetic Variant CMYA5:p.Gly2935Arg (chr5-79737568-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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.

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

Publications

10 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CMYA5	NM_153610.5 link	c.8803G>A	p.Gly2935Arg	missense_variant	Exon 2 of 13	ENST00000446378.3	NP_705838.3	Q8N3K9
CMYA5	XM_047416911.1 link	c.8803G>A	p.Gly2935Arg	missense_variant	Exon 2 of 6		XP_047272867.1
CMYA5	XR_001742036.3 link	n.8875G>A		non_coding_transcript_exon_variant	Exon 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMYA5	ENST00000446378.3 link	c.8803G>A	p.Gly2935Arg	missense_variant	Exon 2 of 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

GnomAD2 exomes

AF:

0.0414

AC:

10239

AN:

247426

AF XY:

0.0442

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 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

African (AFR)

AF:

0.0440

AC:

1472

AN:

33458

American (AMR)

AF:

0.0203

AC:

905

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

3600

AN:

26122

East Asian (EAS)

AF:

0.0908

AC:

3604

AN:

39674

South Asian (SAS)

AF:

0.0780

AC:

6721

AN:

86186

European-Finnish (FIN)

AF:

0.00859

AC:

458

AN:

53346

Middle Eastern (MID)

AF:

0.0735

AC:

424

AN:

5766

European-Non Finnish (NFE)

AF:

0.0265

AC:

29470

AN:

1111730

Other (OTH)

AF:

0.0462

AC:

2788

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

2666

5332

7997

10663

13329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1220

2440

3660

4880

6100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0368

AC:

5598

AN:

152280

Hom.:

149

Cov.:

AF XY:

0.0374

AC XY:

2786

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0423

AC:

1760

AN:

41564

American (AMR)

AF:

0.0226

AC:

345

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

499

AN:

3472

East Asian (EAS)

AF:

0.0997

AC:

517

AN:

5186

South Asian (SAS)

AF:

0.0798

AC:

385

AN:

4822

European-Finnish (FIN)

AF:

0.00867

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0277

AC:

1883

AN:

68016

Other (OTH)

AF:

0.0402

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

276

553

829

1106

1382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0358

Hom.:

432

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

(source)

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

PhyloP100

3.9

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

Mutation Taster

=90/10

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over