dbSNP rs2278240: 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

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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