rs259127

chr5-79762819-A-T

Variant summary

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

The NM_153610.5(CMYA5):c.11408-243A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 456,528 control chromosomes in the GnomAD database, including 10,031 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 0.21 (3461 hom., cov: 32)
  • Exomes 𝑓: 0.20 (6570 hom.)
• Consequence: CMYA5 NM_153610.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

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 (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CMYA5	NM_153610.5	c.11408-243A>T		intron_variant		ENST00000446378.3
CMYA5	XR_001742036.3	n.12153+188A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CMYA5	ENST00000446378.3	c.11408-243A>T		intron_variant		5	NM_153610.5	P1
CMYA5	ENST00000506603.5	n.2893A>T		non_coding_transcript_exon_variant	7/11	1
CMYA5	ENST00000505466.1	n.298-243A>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31662 AN: 151946 Hom.: 3455 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.199

GnomAD4 exome AF: 0.198 AC: 60242 AN: 304464 Hom.: 6570 Cov.: 4 AF XY: 0.194 AC XY: 30580 AN XY: 157326

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.363

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.208 AC: 31694 AN: 152064 Hom.: 3461 Cov.: 32 AF XY: 0.210 AC XY: 15640 AN XY: 74350

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.198

Alfa AF: 0.185 Hom.: 352

Bravo AF: 0.210

Asia WGS AF: 0.276 AC: 961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.2
Dann	Benign	0.83

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: rs259127; hg19: chr5-79058642; COSMIC: COSV71404833;