5-79729205-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.63

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
CMYA5	NM_153610.5	c.440G>A	p.Arg147Gln	missense_variant	2/13	ENST00000446378.3
CMYA5	XM_047416911.1	c.440G>A	p.Arg147Gln	missense_variant	2/6
CMYA5	XR_001742036.3	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	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.: 33

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.: 49 AF XY: 0.00412 AC XY: 554 AN XY: 134352

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.: 34 AF XY: 0.00191 AC XY: 1387 AN XY: 726516

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.: 33 AF XY: 0.0209 AC XY: 1555 AN XY: 74420

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.: 34

Bravo AF: 0.0239

ESP6500AA AF: 0.0707 AC: 262

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00674 AC: 814

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.40
Cadd	Uncertain	25
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.041	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.4	N
REVEL	Benign	0.14
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.058	T
Polyphen		1.0	D
Vest4		0.38
MVP		0.56
MPC		0.22
ClinPred		0.022	T
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

Other links and lift over

dbSNP: rs62621858; hg19: chr5-79025028; COSMIC: COSV71407820;