chr5-79728924-C-A

Variant names:

• chr5-79728924-C-A
• rs189499447
• NM_153610.5:c.159C>A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_153610.5(CMYA5):​c.159C>A​(p.Asp53Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00641 in 1,547,718 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0066 (38 hom.)
• Consequence: CMYA5 NM_153610.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.54

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0061644316).
• BP6: Variant 5-79728924-C-A is Benign according to our data. Variant chr5-79728924-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 778322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMYA5	NM_153610.5	c.159C>A	p.Asp53Glu	missense_variant	Exon 2 of 13	ENST00000446378.3	NP_705838.3
CMYA5	XM_047416911.1	c.159C>A	p.Asp53Glu	missense_variant	Exon 2 of 6		XP_047272867.1
CMYA5	XR_001742036.3	n.231C>A		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.159C>A	p.Asp53Glu	missense_variant	Exon 2 of 13	5	NM_153610.5	ENSP00000394770.2

Frequencies

GnomAD3 genomes AF: 0.00510 AC: 775 AN: 151838 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00932

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00114

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00778

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00426 AC: 943 AN: 221340 Hom.: 4 AF XY: 0.00412 AC XY: 497 AN XY: 120580

Gnomad AFR exome AF: 0.00161

Gnomad AMR exome AF: 0.00394

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000204

Gnomad FIN exome AF: 0.000916

Gnomad NFE exome AF: 0.00720

Gnomad OTH exome AF: 0.00447

GnomAD4 exome AF: 0.00656 AC: 9150 AN: 1395762 Hom.: 38 Cov.: 29 AF XY: 0.00638 AC XY: 4417 AN XY: 692494

Gnomad4 AFR exome AF: 0.00146

Gnomad4 AMR exome AF: 0.00413

Gnomad4 ASJ exome AF: 0.00148

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000328

Gnomad4 FIN exome AF: 0.00144

Gnomad4 NFE exome AF: 0.00783

Gnomad4 OTH exome AF: 0.00650

GnomAD4 genome AF: 0.00510 AC: 775 AN: 151956 Hom.: 2 Cov.: 32 AF XY: 0.00465 AC XY: 345 AN XY: 74272

Gnomad4 AFR AF: 0.00181

Gnomad4 AMR AF: 0.00931

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00114

Gnomad4 NFE AF: 0.00778

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00626 Hom.: 6

Bravo AF: 0.00536

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00727 AC: 28

ESP6500AA AF: 0.00192 AC: 7

ESP6500EA AF: 0.00625 AC: 51

ExAC AF: 0.00407 AC: 491

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CMYA5: BS2 -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.0062	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.12
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.95	P
Vest4		0.24
MutPred		0.069		Gain of helix (P = 0.0425);
MVP		0.21
MPC		0.25
ClinPred		0.030	T
GERP RS		0.83
Varity_R		0.15
gMVP		0.031

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs189499447; hg19: chr5-79024747;