5-79729105-G-A

Variant names:

• chr5-79729105-G-A
• NM_153610.5:c.340G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153610.5(CMYA5):​c.340G>A​(p.Val114Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CMYA5 NM_153610.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00100
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04862091).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153610.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMYA5	NM_153610.5	MANE Select	c.340G>A	p.Val114Met	missense	Exon 2 of 13	NP_705838.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMYA5	ENST00000446378.3	TSL:5 MANE Select	c.340G>A	p.Val114Met	missense	Exon 2 of 13	ENSP00000394770.2	Q8N3K9
	CMYA5	ENST00000940891.1		c.340G>A	p.Val114Met	missense	Exon 2 of 13	ENSP00000610950.1
	CMYA5	ENST00000856934.1		c.223-14722G>A		intron	N/A	ENSP00000526993.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.2
DANN	Benign	0.94
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.0010
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.098
Sift	Benign	0.13	T
Sift4G	Benign	0.11	T
Polyphen		0.59	P
Vest4		0.083
MutPred		0.15		Loss of catalytic residue at V114 (P = 0.0012)
MVP		0.16
MPC		0.055
ClinPred		0.12	T
GERP RS		-3.8
Varity_R		0.035
gMVP		0.097
Mutation Taster		=96/4	polymorphism

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

hg19: chr5-79024928;