rs259127

Variant names:

• chr5-79762819-A-T
• rs259127
• ENST00000506603.5:n.2893A>T

Variant summary

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

The ENST00000506603.5(CMYA5):​n.2893A>T variant causes a non coding transcript exon 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 ENST00000506603.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• Publications: 3 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 (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 rank	MANE	Protein	UniProt
CMYA5	NM_153610.5	c.11408-243A>T		intron_variant	Intron 8 of 12	ENST00000446378.3	NP_705838.3
CMYA5	XR_001742036.3	n.12153+188A>T		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMYA5	ENST00000506603.5	n.2893A>T		non_coding_transcript_exon_variant	Exon 7 of 11	1
CMYA5	ENST00000446378.3	c.11408-243A>T		intron_variant	Intron 8 of 12	5	NM_153610.5	ENSP00000394770.2
CMYA5	ENST00000505466.1	n.298-243A>T		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.252 AC: 2475 AN: 9822

American (AMR) AF: 0.141 AC: 1567 AN: 11086

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 1542 AN: 10336

East Asian (EAS) AF: 0.363 AC: 8832 AN: 24300

South Asian (SAS) AF: 0.152 AC: 2734 AN: 17952

European-Finnish (FIN) AF: 0.210 AC: 4286 AN: 20400

Middle Eastern (MID) AF: 0.158 AC: 227 AN: 1434

European-Non Finnish (NFE) AF: 0.183 AC: 34905 AN: 190288

Other (OTH) AF: 0.195 AC: 3674 AN: 18846

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

African (AFR) AF: 0.251 AC: 10391 AN: 41462

American (AMR) AF: 0.162 AC: 2476 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 582 AN: 3470

East Asian (EAS) AF: 0.353 AC: 1828 AN: 5176

South Asian (SAS) AF: 0.171 AC: 824 AN: 4820

European-Finnish (FIN) AF: 0.226 AC: 2394 AN: 10590

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.185 AC: 12596 AN: 67958

Other (OTH) AF: 0.198 AC: 416 AN: 2106

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
PhyloP100		0.0090
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: rs259127; hg19: chr5-79058642; COSMIC: COSV71404833;