Variant 5-79729205-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153610.5(CMYA5):c.440G>A(p.Arg147Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00406 in 1,612,770 control chromosomes in the GnomAD database, including 245 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 130 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 115 hom. )

Consequence

CMYA5
NM_153610.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.63

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025502741).

BP6

Variant 5-79729205-G-A is Benign according to our data. Variant chr5-79729205-G-A is described in ClinVar as [Benign]. Clinvar id is 785129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CMYA5	NM_153610.5 linkuse as main transcript	c.440G>A	p.Arg147Gln	missense_variant	2/13	ENST00000446378.3
CMYA5	XM_047416911.1 linkuse as main transcript	c.440G>A	p.Arg147Gln	missense_variant	2/6
CMYA5	XR_001742036.3 linkuse as main transcript	n.512G>A		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CMYA5	ENST00000446378.3 linkuse as main transcript	c.440G>A	p.Arg147Gln	missense_variant	2/13	5	NM_153610.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3322

AN:

152086

Hom.:

130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0767

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00727

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00542

AC:

1342

AN:

247774

Hom.:

AF XY:

0.00412

AC XY:

554

AN XY:

134352

show subpopulations

Gnomad AFR exome

AF:

0.0754

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.000501

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.000232

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000373

Gnomad OTH exome

AF:

0.00266

GnomAD4 exome

AF:

0.00221

AC:

3230

AN:

1460566

Hom.:

115

Cov.:

AF XY:

0.00191

AC XY:

1387

AN XY:

726516

show subpopulations

Gnomad4 AFR exome

AF:

0.0782

Gnomad4 AMR exome

AF:

0.00335

Gnomad4 ASJ exome

AF:

0.000690

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000256

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000136

Gnomad4 OTH exome

AF:

0.00431

GnomAD4 genome

AF:

0.0218

AC:

3325

AN:

152204

Hom.:

130

Cov.:

AF XY:

0.0209

AC XY:

1555

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0766

Gnomad4 AMR

AF:

0.00726

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.00387

Hom.:

Bravo

AF:

0.0239

ESP6500AA

AF:

0.0707

AC:

262

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00674

AC:

814

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.041

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-2.4

REVEL

Benign

0.14

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.058

Polyphen

1.0

Vest4

0.38

MVP

0.56

MPC

0.22

ClinPred

0.022

GERP RS

5.5

Varity_R

0.14

gMVP

0.24

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over