Variant 5-79729321-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_153610.5(CMYA5):c.556A>G(p.Thr186Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000875 in 1,612,220 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000088 ( 2 hom. )

Consequence

CMYA5
NM_153610.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0160

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004248798).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CMYA5	NM_153610.5 linkuse as main transcript	c.556A>G	p.Thr186Ala	missense_variant	2/13	ENST00000446378.3
CMYA5	XM_047416911.1 linkuse as main transcript	c.556A>G	p.Thr186Ala	missense_variant	2/6
CMYA5	XR_001742036.3 linkuse as main transcript	n.628A>G		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.556A>G	p.Thr186Ala	missense_variant	2/13	5	NM_153610.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000215

AC:

AN:

246430

Hom.:

AF XY:

0.000239

AC XY:

AN XY:

133634

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00231

Gnomad SAS exome

AF:

0.000301

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000335

GnomAD4 exome

AF:

0.0000884

AC:

129

AN:

1459880

Hom.:

Cov.:

AF XY:

0.000112

AC XY:

AN XY:

726208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00161

Gnomad4 SAS exome

AF:

0.000467

Gnomad4 FIN exome

AF:

0.0000937

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000109

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.000199

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2022

The c.556A>G (p.T186A) alteration is located in exon 2 (coding exon 2) of the CMYA5 gene. This alteration results from a A to G substitution at nucleotide position 556, causing the threonine (T) at amino acid position 186 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.75

Cadd

Benign

0.29

Dann

Benign

0.66

DEOGEN2

Benign

0.020

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.46

M_CAP

Benign

0.0068

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.1

REVEL

Benign

0.024

Sift

Benign

0.48

Sift4G

Benign

0.65

Polyphen

0.0050

Vest4

0.016

MutPred

0.18

Loss of phosphorylation at T186 (P = 0.0474);

MVP

0.055

MPC

0.054

ClinPred

0.019

GERP RS

-7.1

Varity_R

0.035

gMVP

0.061

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