5-79729105-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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

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 Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMYA5	NM_153610.5	c.340G>A	p.Val114Met	missense_variant	Exon 2 of 13	ENST00000446378.3	NP_705838.3
CMYA5	XM_047416911.1	c.340G>A	p.Val114Met	missense_variant	Exon 2 of 6		XP_047272867.1
CMYA5	XR_001742036.3	n.412G>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.340G>A	p.Val114Met	missense_variant	Exon 2 of 13	5	NM_153610.5	ENSP00000394770.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.340G>A (p.V114M) alteration is located in exon 2 (coding exon 2) of the CMYA5 gene. This alteration results from a G to A substitution at nucleotide position 340, causing the valine (V) at amino acid position 114 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-79024928;