5-79729214-A-G

Position:

• chr5-79729214-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153610.5(CMYA5):​c.449A>G​(p.Asn150Ser) 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: -0.0140

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=0.026364356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMYA5	NM_153610.5	c.449A>G	p.Asn150Ser	missense_variant	2/13	ENST00000446378.3	NP_705838.3
CMYA5	XM_047416911.1	c.449A>G	p.Asn150Ser	missense_variant	2/6		XP_047272867.1
CMYA5	XR_001742036.3	n.521A>G		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMYA5	ENST00000446378.3	c.449A>G	p.Asn150Ser	missense_variant	2/13	5	NM_153610.5	ENSP00000394770	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

The c.449A>G (p.N150S) alteration is located in exon 2 (coding exon 2) of the CMYA5 gene. This alteration results from a A to G substitution at nucleotide position 449, causing the asparagine (N) at amino acid position 150 to be replaced by a serine (S). 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	0.084
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.5
DANN	Benign	0.96
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.14	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.067
Sift	Benign	0.52	T
Sift4G	Benign	0.33	T
Polyphen		0.31	B
Vest4		0.12
MutPred		0.19		Gain of phosphorylation at N150 (P = 7e-04);
MVP		0.16
MPC		0.049
ClinPred		0.087	T
GERP RS		-0.78
Varity_R		0.036
gMVP		0.073

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: chr5-79025037;