Variant 5-79738839-C-G 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.10074C>G(p.His3358Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0875 in 1,613,660 control chromosomes in the GnomAD database, including 10,935 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 0.13 ( 1904 hom., cov: 32)

Exomes 𝑓: 0.084 ( 9031 hom. )

Consequence

CMYA5
NM_153610.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.101

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003689319).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CMYA5	NM_153610.5 linkuse as main transcript	c.10074C>G	p.His3358Gln	missense_variant	2/13	ENST00000446378.3	NP_705838.3
CMYA5	XM_047416911.1 linkuse as main transcript	c.10074C>G	p.His3358Gln	missense_variant	2/6		XP_047272867.1
CMYA5	XR_001742036.3 linkuse as main transcript	n.10146C>G		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.10074C>G	p.His3358Gln	missense_variant	2/13	5	NM_153610.5	ENSP00000394770	P1
CMYA5	ENST00000506603.5 linkuse as main transcript	n.698C>G		non_coding_transcript_exon_variant	1/11	1

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

18996

AN:

151966

Hom.:

1887

Cov.:

show subpopulations

Gnomad AFR

AF:

0.234

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0552

Gnomad ASJ

AF:

0.0568

Gnomad EAS

AF:

0.405

Gnomad SAS

AF:

0.0914

Gnomad FIN

AF:

0.0977

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0661

Gnomad OTH

AF:

0.0955

GnomAD3 exomes

AF:

0.104

AC:

25806

AN:

248930

Hom.:

2569

AF XY:

0.0991

AC XY:

13383

AN XY:

135042

show subpopulations

Gnomad AFR exome

AF:

0.237

Gnomad AMR exome

AF:

0.0360

Gnomad ASJ exome

AF:

0.0520

Gnomad EAS exome

AF:

0.410

Gnomad SAS exome

AF:

0.0947

Gnomad FIN exome

AF:

0.0989

Gnomad NFE exome

AF:

0.0667

Gnomad OTH exome

AF:

0.0767

GnomAD4 exome

AF:

0.0836

AC:

122158

AN:

1461576

Hom.:

9031

Cov.:

AF XY:

0.0830

AC XY:

60346

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.245

Gnomad4 AMR exome

AF:

0.0383

Gnomad4 ASJ exome

AF:

0.0550

Gnomad4 EAS exome

AF:

0.465

Gnomad4 SAS exome

AF:

0.0932

Gnomad4 FIN exome

AF:

0.0985

Gnomad4 NFE exome

AF:

0.0659

Gnomad4 OTH exome

AF:

0.0921

GnomAD4 genome

AF:

0.125

AC:

19059

AN:

152084

Hom.:

1904

Cov.:

AF XY:

0.128

AC XY:

9551

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.235

Gnomad4 AMR

AF:

0.0550

Gnomad4 ASJ

AF:

0.0568

Gnomad4 EAS

AF:

0.405

Gnomad4 SAS

AF:

0.0914

Gnomad4 FIN

AF:

0.0977

Gnomad4 NFE

AF:

0.0661

Gnomad4 OTH

AF:

0.0945

Alfa

AF:

0.0726

Hom.:

564

Bravo

AF:

0.129

TwinsUK

AF:

0.0696

AC:

258

ALSPAC

AF:

0.0654

AC:

252

ESP6500AA

AF:

0.225

AC:

933

ESP6500EA

AF:

0.0658

AC:

555

ExAC

AF:

0.107

AC:

12994

EpiCase

AF:

0.0609

EpiControl

AF:

0.0563

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.0

DANN

Benign

0.26

DEOGEN2

Benign

0.020

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00092

LIST_S2

Benign

0.16

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

2.6

REVEL

Benign

0.040

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.027

MutPred

0.16

Loss of glycosylation at S3357 (P = 0.1338);

MPC

0.055

ClinPred

0.000019

GERP RS

2.2

Varity_R

0.026

gMVP

0.098

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