Variant 5-79728924-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_153610.5(CMYA5):c.159C>A(p.Asp53Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00641 in 1,547,718 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 38 hom. )

Consequence

CMYA5
NM_153610.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.54

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061644316).

BP6

Variant 5-79728924-C-A is Benign according to our data. Variant chr5-79728924-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 778322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CMYA5	NM_153610.5 linkuse as main transcript	c.159C>A	p.Asp53Glu	missense_variant	2/13	ENST00000446378.3
CMYA5	XM_047416911.1 linkuse as main transcript	c.159C>A	p.Asp53Glu	missense_variant	2/6
CMYA5	XR_001742036.3 linkuse as main transcript	n.231C>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.159C>A	p.Asp53Glu	missense_variant	2/13	5	NM_153610.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00510

AC:

775

AN:

151838

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00932

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00114

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00778

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00426

AC:

943

AN:

221340

Hom.:

AF XY:

0.00412

AC XY:

497

AN XY:

120580

show subpopulations

Gnomad AFR exome

AF:

0.00161

Gnomad AMR exome

AF:

0.00394

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000204

Gnomad FIN exome

AF:

0.000916

Gnomad NFE exome

AF:

0.00720

Gnomad OTH exome

AF:

0.00447

GnomAD4 exome

AF:

0.00656

AC:

9150

AN:

1395762

Hom.:

Cov.:

AF XY:

0.00638

AC XY:

4417

AN XY:

692494

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00413

Gnomad4 ASJ exome

AF:

0.00148

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000328

Gnomad4 FIN exome

AF:

0.00144

Gnomad4 NFE exome

AF:

0.00783

Gnomad4 OTH exome

AF:

0.00650

GnomAD4 genome

AF:

0.00510

AC:

775

AN:

151956

Hom.:

Cov.:

AF XY:

0.00465

AC XY:

345

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.00181

Gnomad4 AMR

AF:

0.00931

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00114

Gnomad4 NFE

AF:

0.00778

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00626

Hom.:

Bravo

AF:

0.00536

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00192

AC:

ESP6500EA

AF:

0.00625

AC:

ExAC

AF:

0.00407

AC:

491

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	CMYA5: BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.56

M_CAP

Benign

0.020

MetaRNN

Benign

0.0062

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.9

REVEL

Benign

0.12

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0

Polyphen

0.95

Vest4

0.24

MutPred

0.069

Gain of helix (P = 0.0425);

MVP

0.21

MPC

0.25

ClinPred

0.030

GERP RS

0.83

Varity_R

0.15

gMVP

0.031

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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