rs2278240

chr5-79737568-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153610.5(CMYA5):c.8803G>A(p.Gly2935Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0341 in 1,613,564 control chromosomes in the GnomAD database, including 1,453 homozygotes. In-silico tool predicts 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 0.037 (149 hom., cov: 32)
  • Exomes 𝑓: 0.034 (1304 hom.)
• Consequence: CMYA5 NM_153610.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.89

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013951659).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CMYA5	NM_153610.5	c.8803G>A	p.Gly2935Arg	missense_variant	2/13	ENST00000446378.3
CMYA5	XM_047416911.1	c.8803G>A	p.Gly2935Arg	missense_variant	2/6
CMYA5	XR_001742036.3	n.8875G>A		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CMYA5	ENST00000446378.3	c.8803G>A	p.Gly2935Arg	missense_variant	2/13	5	NM_153610.5	P1

Frequencies

GnomAD3 genomes AF: 0.0368 AC: 5592 AN: 152162 Hom.: 150 Cov.: 32

Gnomad AFR AF: 0.0424

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0227

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0998

Gnomad SAS AF: 0.0796

Gnomad FIN AF: 0.00867

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0277

Gnomad OTH AF: 0.0377

GnomAD3 exomes AF: 0.0414 AC: 10239 AN: 247426 Hom.: 376 AF XY: 0.0442 AC XY: 5941 AN XY: 134270

Gnomad AFR exome AF: 0.0439

Gnomad AMR exome AF: 0.0196

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.0907

Gnomad SAS exome AF: 0.0751

Gnomad FIN exome AF: 0.00707

Gnomad NFE exome AF: 0.0281

Gnomad OTH exome AF: 0.0458

GnomAD4 exome AF: 0.0338 AC: 49442 AN: 1461284 Hom.: 1304 Cov.: 35 AF XY: 0.0358 AC XY: 26002 AN XY: 726874

Gnomad4 AFR exome AF: 0.0440

Gnomad4 AMR exome AF: 0.0203

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.0908

Gnomad4 SAS exome AF: 0.0780

Gnomad4 FIN exome AF: 0.00859

Gnomad4 NFE exome AF: 0.0265

Gnomad4 OTH exome AF: 0.0462

GnomAD4 genome AF: 0.0368 AC: 5598 AN: 152280 Hom.: 149 Cov.: 32 AF XY: 0.0374 AC XY: 2786 AN XY: 74444

Gnomad4 AFR AF: 0.0423

Gnomad4 AMR AF: 0.0226

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.0997

Gnomad4 SAS AF: 0.0798

Gnomad4 FIN AF: 0.00867

Gnomad4 NFE AF: 0.0277

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0360 Hom.: 327

Bravo AF: 0.0370

TwinsUK AF: 0.0264 AC: 98

ALSPAC AF: 0.0309 AC: 119

ESP6500AA AF: 0.0402 AC: 149

ESP6500EA AF: 0.0347 AC: 284

ExAC AF: 0.0409 AC: 4936

Asia WGS AF: 0.100 AC: 347 AN: 3478

EpiCase AF: 0.0328

EpiControl AF: 0.0352

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.52
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.063	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	0.98	N
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.018	D
Polyphen		0.99	D
Vest4		0.094
MutPred		0.17		Gain of solvent accessibility (P = 0.019);
MPC		0.38
ClinPred		0.044	T
GERP RS		5.1
Varity_R		0.64
gMVP		0.36

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: rs2278240; hg19: chr5-79033391; COSMIC: COSV71405980; COSMIC: COSV71405980;