5-79690010-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153610.5(CMYA5):c.103G>A(p.Glu35Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,484,580 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (71 hom.)
• Consequence: CMYA5 NM_153610.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.33

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004689783).
• BP6: Variant 5-79690010-G-A is Benign according to our data. Variant chr5-79690010-G-A is described in ClinVar as [Benign]. Clinvar id is 791626.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CMYA5	NM_153610.5	c.103G>A	p.Glu35Lys	missense_variant	1/13	ENST00000446378.3
CMYA5	XM_047416911.1	c.103G>A	p.Glu35Lys	missense_variant	1/6
CMYA5	XR_001742036.3	n.175G>A		non_coding_transcript_exon_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CMYA5	ENST00000446378.3	c.103G>A	p.Glu35Lys	missense_variant	1/13	5	NM_153610.5	P1

Frequencies

GnomAD3 genomes AF: 0.00306 AC: 466 AN: 152230 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0477

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00301

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00170

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00401 AC: 391 AN: 97422 Hom.: 11 AF XY: 0.00374 AC XY: 194 AN XY: 51922

Gnomad AFR exome AF: 0.000317

Gnomad AMR exome AF: 0.00118

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0443

Gnomad SAS exome AF: 0.00205

Gnomad FIN exome AF: 0.00292

Gnomad NFE exome AF: 0.00179

Gnomad OTH exome AF: 0.00296

GnomAD4 exome AF: 0.00303 AC: 4037 AN: 1332232 Hom.: 71 Cov.: 26 AF XY: 0.00295 AC XY: 1937 AN XY: 655614

Gnomad4 AFR exome AF: 0.000406

Gnomad4 AMR exome AF: 0.00138

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0563

Gnomad4 SAS exome AF: 0.00208

Gnomad4 FIN exome AF: 0.00321

Gnomad4 NFE exome AF: 0.00173

Gnomad4 OTH exome AF: 0.00259

GnomAD4 genome AF: 0.00306 AC: 466 AN: 152348 Hom.: 11 Cov.: 32 AF XY: 0.00357 AC XY: 266 AN XY: 74496

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0478

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00301

Gnomad4 NFE AF: 0.00170

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00139 Hom.: 1

Bravo AF: 0.00361

ESP6500AA AF: 0.000288 AC: 1

ESP6500EA AF: 0.00130 AC: 9

ExAC AF: 0.00200 AC: 91

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.45
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Benign	0.074
Eigen_PC	Benign	0.053
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.070
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.054	T
Polyphen		0.98	D
Vest4		0.26
MVP		0.34
MPC		0.24
ClinPred		0.033	T
GERP RS		3.2
Varity_R		0.31
gMVP		0.12

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: rs141830505; hg19: chr5-78985833; COSMIC: COSV99706307; COSMIC: COSV99706307;