rs13158477

Variant names:

• chr5-79732903-A-G
• rs13158477
• NM_153610.5:c.4138A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153610.5(CMYA5):​c.4138A>G​(p.Ile1380Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,613,318 control chromosomes in the GnomAD database, including 19,313 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1653 hom., cov: 33)
  • Exomes 𝑓: 0.15 (17660 hom.)
• Consequence: CMYA5 NM_153610.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.998
• Publications: 19 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=0.0015851259).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMYA5	NM_153610.5	c.4138A>G	p.Ile1380Val	missense_variant	Exon 2 of 13	ENST00000446378.3	NP_705838.3
CMYA5	XM_047416911.1	c.4138A>G	p.Ile1380Val	missense_variant	Exon 2 of 6		XP_047272867.1
CMYA5	XR_001742036.3	n.4210A>G		non_coding_transcript_exon_variant	Exon 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMYA5	ENST00000446378.3	c.4138A>G	p.Ile1380Val	missense_variant	Exon 2 of 13	5	NM_153610.5	ENSP00000394770.2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21879 AN: 152140 Hom.: 1654 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.147

GnomAD2 exomes AF: 0.137 AC: 34030 AN: 247868 AF XY: 0.139

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.0113

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.152 AC: 222790 AN: 1461060 Hom.: 17660 Cov.: 39 AF XY: 0.152 AC XY: 110367 AN XY: 726802

African (AFR) AF: 0.126 AC: 4212 AN: 33470

American (AMR) AF: 0.110 AC: 4918 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 3976 AN: 26126

East Asian (EAS) AF: 0.0245 AC: 973 AN: 39672

South Asian (SAS) AF: 0.130 AC: 11242 AN: 86204

European-Finnish (FIN) AF: 0.190 AC: 10113 AN: 53360

Middle Eastern (MID) AF: 0.165 AC: 954 AN: 5766

European-Non Finnish (NFE) AF: 0.160 AC: 177362 AN: 1111456

Other (OTH) AF: 0.150 AC: 9040 AN: 60346

GnomAD4 genome AF: 0.144 AC: 21882 AN: 152258 Hom.: 1653 Cov.: 33 AF XY: 0.141 AC XY: 10526 AN XY: 74446

African (AFR) AF: 0.127 AC: 5272 AN: 41562

American (AMR) AF: 0.124 AC: 1890 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 535 AN: 3472

East Asian (EAS) AF: 0.0181 AC: 94 AN: 5186

South Asian (SAS) AF: 0.124 AC: 599 AN: 4822

European-Finnish (FIN) AF: 0.196 AC: 2075 AN: 10600

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10854 AN: 68002

Other (OTH) AF: 0.145 AC: 306 AN: 2116

Alfa AF: 0.153 Hom.: 8723

Bravo AF: 0.138

TwinsUK AF: 0.149 AC: 553

ALSPAC AF: 0.161 AC: 622

ESP6500AA AF: 0.126 AC: 469

ESP6500EA AF: 0.157 AC: 1285

ExAC AF: 0.137 AC: 16597

Asia WGS AF: 0.0870 AC: 305 AN: 3478

EpiCase AF: 0.162

EpiControl AF: 0.153

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.89	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.052
DANN	Benign	0.13
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-1.0
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.53	N
REVEL	Benign	0.054
Sift	Benign	0.69	T
Sift4G	Benign	0.57	T
Polyphen		0.0010	B
Vest4		0.0010
MPC		0.048
ClinPred		0.0028	T
GERP RS		-0.88
Varity_R		0.025
gMVP		0.064
Mutation Taster		=100/0	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: rs13158477; hg19: chr5-79028726; COSMIC: COSV71404120;