rs2278240

Variant names:

• chr5-79737568-G-A
• rs2278240
• NM_153610.5:c.8803G>A

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153610.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMYA5	NM_153610.5	MANE Select	c.8803G>A	p.Gly2935Arg	missense	Exon 2 of 13	NP_705838.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMYA5	ENST00000446378.3	TSL:5 MANE Select	c.8803G>A	p.Gly2935Arg	missense	Exon 2 of 13	ENSP00000394770.2	Q8N3K9
	CMYA5	ENST00000940891.1		c.526-6259G>A		intron	N/A	ENSP00000610950.1
	CMYA5	ENST00000856934.1		c.223-6259G>A		intron	N/A	ENSP00000526993.1

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

GnomAD2 exomes AF: 0.0414 AC: 10239 AN: 247426 AF XY: 0.0442

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 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

African (AFR) AF: 0.0440 AC: 1472 AN: 33458

American (AMR) AF: 0.0203 AC: 905 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 3600 AN: 26122

East Asian (EAS) AF: 0.0908 AC: 3604 AN: 39674

South Asian (SAS) AF: 0.0780 AC: 6721 AN: 86186

European-Finnish (FIN) AF: 0.00859 AC: 458 AN: 53346

Middle Eastern (MID) AF: 0.0735 AC: 424 AN: 5766

European-Non Finnish (NFE) AF: 0.0265 AC: 29470 AN: 1111730

Other (OTH) AF: 0.0462 AC: 2788 AN: 60358

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

African (AFR) AF: 0.0423 AC: 1760 AN: 41564

American (AMR) AF: 0.0226 AC: 345 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 499 AN: 3472

East Asian (EAS) AF: 0.0997 AC: 517 AN: 5186

South Asian (SAS) AF: 0.0798 AC: 385 AN: 4822

European-Finnish (FIN) AF: 0.00867 AC: 92 AN: 10614

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0277 AC: 1883 AN: 68016

Other (OTH) AF: 0.0402 AC: 85 AN: 2116

Alfa AF: 0.0358 Hom.: 432

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 v4.9

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
PhyloP100		3.9
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
Mutation Taster		=90/10	polymorphism (auto)

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

Other links and lift over

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