rs3749679

Positions:

• chr5-79743492-T-C

Variant summary

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

The NM_153610.5(CMYA5):​c.10639-335T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 152,248 control chromosomes in the GnomAD database, including 82 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 0.011 (82 hom., cov: 32)
• Consequence: CMYA5 NM_153610.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157

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]

CMYA5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMYA5	NM_153610.5	c.10639-335T>C		intron_variant		ENST00000446378.3	NP_705838.3
CMYA5	XM_047416911.1	c.10639-335T>C		intron_variant			XP_047272867.1
CMYA5	XR_001742036.3	n.10711-335T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMYA5	ENST00000446378.3	c.10639-335T>C		intron_variant		5	NM_153610.5	ENSP00000394770.2
CMYA5	ENST00000506603.5	n.1263-335T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1705 AN: 152130 Hom.: 82 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.0696

Gnomad FIN AF: 0.00725

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00440

Gnomad OTH AF: 0.00908

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0112 AC: 1705 AN: 152248 Hom.: 82 Cov.: 32 AF XY: 0.0133 AC XY: 993 AN XY: 74438

Gnomad4 AFR AF: 0.00108

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.0696

Gnomad4 FIN AF: 0.00725

Gnomad4 NFE AF: 0.00440

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00551 Hom.: 3

Bravo AF: 0.0103

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.5
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3749679; hg19: chr5-79039315;