rs147271727

Variant names:

• chr5-79729078-G-C
• rs147271727
• NM_153610.5:c.313G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_153610.5(CMYA5):​c.313G>C​(p.Gly105Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000339 in 1,613,900 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G105G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (1 hom.)
• Consequence: CMYA5 NM_153610.5 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 7.25
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0073223114).
• BP6: Variant 5-79729078-G-C is Benign according to our data. Variant chr5-79729078-G-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 716935.

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.313G>C	p.Gly105Arg	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.313G>C	p.Gly105Arg	missense	Exon 2 of 13	ENSP00000394770.2	Q8N3K9
	CMYA5	ENST00000940891.1		c.313G>C	p.Gly105Arg	missense	Exon 2 of 13	ENSP00000610950.1
	CMYA5	ENST00000856934.1		c.223-14749G>C		intron	N/A	ENSP00000526993.1

Frequencies

GnomAD3 genomes AF: 0.00169 AC: 257 AN: 152106 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00594

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000530 AC: 132 AN: 249126 AF XY: 0.000355

Gnomad AFR exome AF: 0.00736

Gnomad AMR exome AF: 0.000377

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000198 AC: 289 AN: 1461676 Hom.: 1 Cov.: 33 AF XY: 0.000173 AC XY: 126 AN XY: 727120

African (AFR) AF: 0.00699 AC: 234 AN: 33478

American (AMR) AF: 0.000313 AC: 14 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111850

Other (OTH) AF: 0.000414 AC: 25 AN: 60372

GnomAD4 genome AF: 0.00169 AC: 258 AN: 152224 Hom.: 1 Cov.: 32 AF XY: 0.00176 AC XY: 131 AN XY: 74420

African (AFR) AF: 0.00595 AC: 247 AN: 41544

American (AMR) AF: 0.000458 AC: 7 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000172 Hom.: 0

Bravo AF: 0.00193

ESP6500AA AF: 0.00773 AC: 29

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000546 AC: 66

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.037	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.0073	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.4	L
PhyloP100		7.3
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.36
MVP		0.63
MPC		0.38
ClinPred		0.059	T
GERP RS		5.6
Varity_R		0.38
gMVP		0.14
Mutation Taster		=86/14	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

dbSNP: rs147271727; hg19: chr5-79024901;