dbSNP rs10043986: CMYA5:p.Pro4063Leu (chr5-79799594-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_153610.5(CMYA5):c.12188C>T(p.Pro4063Leu) variant causes a missense change. The variant allele was found at a frequency of 0.106 in 1,612,348 control chromosomes in the GnomAD database, including 10,004 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.081 ( 664 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9340 hom. )

Consequence

CMYA5
NM_153610.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.79

Publications

20 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:

ENSG00000250258 (HGNC:):

ENSG00000250258 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019601285).

BP6

Variant 5-79799594-C-T is Benign according to our data. Variant chr5-79799594-C-T is described in ClinVar as Benign. ClinVar VariationId is 1232412.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMYA5	NM_153610.5 link	c.12188C>T	p.Pro4063Leu	missense_variant	Exon 13 of 13	ENST00000446378.3	NP_705838.3	Q8N3K9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CMYA5	ENST00000446378.3 link	c.12188C>T	p.Pro4063Leu	missense_variant	Exon 13 of 13	5	NM_153610.5	ENSP00000394770.2	Q8N3K9
CMYA5	ENST00000506603.5 link	n.3916C>T		non_coding_transcript_exon_variant	Exon 11 of 11	1
ENSG00000250258	ENST00000421252.2 link	n.235+2011G>A		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.0815

AC:

12390

AN:

152074

Hom.:

663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0215

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0789

Gnomad ASJ

AF:

0.0946

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.0620

Gnomad FIN

AF:

0.0897

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.0910

GnomAD2 exomes

AF:

0.0866

AC:

21320

AN:

246112

AF XY:

0.0901

show subpopulations

Gnomad AFR exome

AF:

0.0188

Gnomad AMR exome

AF:

0.0504

Gnomad ASJ exome

AF:

0.0916

Gnomad EAS exome

AF:

0.000281

Gnomad FIN exome

AF:

0.0892

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.0853

GnomAD4 exome

AF:

0.108

AC:

157848

AN:

1460156

Hom.:

9340

Cov.:

AF XY:

0.108

AC XY:

78179

AN XY:

726164

show subpopulations

African (AFR)

AF:

0.0175

AC:

586

AN:

33464

American (AMR)

AF:

0.0532

AC:

2370

AN:

44560

Ashkenazi Jewish (ASJ)

AF:

0.0977

AC:

2550

AN:

26088

East Asian (EAS)

AF:

0.000328

AC:

AN:

39664

South Asian (SAS)

AF:

0.0653

AC:

5617

AN:

85982

European-Finnish (FIN)

AF:

0.0898

AC:

4789

AN:

53324

Middle Eastern (MID)

AF:

0.0898

AC:

518

AN:

5766

European-Non Finnish (NFE)

AF:

0.122

AC:

135459

AN:

1110998

Other (OTH)

AF:

0.0986

AC:

5946

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

7112

14224

21336

28448

35560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4750

9500

14250

19000

23750

<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:

0.0814

AC:

12387

AN:

152192

Hom.:

664

Cov.:

AF XY:

0.0778

AC XY:

5790

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0214

AC:

890

AN:

41536

American (AMR)

AF:

0.0790

AC:

1208

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0946

AC:

328

AN:

3468

East Asian (EAS)

AF:

0.000581

AC:

AN:

5166

South Asian (SAS)

AF:

0.0617

AC:

297

AN:

4816

European-Finnish (FIN)

AF:

0.0897

AC:

951

AN:

10604

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.124

AC:

8432

AN:

67996

Other (OTH)

AF:

0.0891

AC:

188

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

577

1154

1732

2309

2886

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

150

300

450

600

750

<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:

0.109

Hom.:

3713

Bravo

AF:

0.0769

TwinsUK

AF:

0.119

AC:

441

ALSPAC

AF:

0.117

AC:

452

ESP6500AA

AF:

0.0254

AC:

ESP6500EA

AF:

0.119

AC:

978

ExAC

AF:

0.0881

AC:

10641

Asia WGS

AF:

0.0290

AC:

101

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 20, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 20838396, 30658136) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.55

MutationAssessor

Pathogenic

3.4

PhyloP100

6.8

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-6.9

REVEL

Uncertain

0.54

Sift

Uncertain

0.0090

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.30

MPC

0.36

ClinPred

0.066

GERP RS

6.0

Varity_R

0.31

gMVP

0.80

Mutation Taster

=59/41

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over