NM_153610.5:c.12188C>T

Variant names:

• chr5-79799594-C-T
• rs10043986
• NM_153610.5:c.12188C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153610.5(CMYA5):​c.12188C>T​(p.Pro4063Leu) variant causes a missense change. The variant allele was found at a frequency of 0.106 in 1,612,348 control chromosomes in the GnomAD database, including 10,004 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.081 (664 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9340 hom.)
• Consequence: CMYA5 NM_153610.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.79
• Publications: 20 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]

ENSG00000250258 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019601285).
• BP6: Variant 5-79799594-C-T is Benign according to our data. Variant chr5-79799594-C-T is described in ClinVar as Benign. ClinVar VariationId is 1232412.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

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.12188C>T	p.Pro4063Leu	missense	Exon 13 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.12188C>T	p.Pro4063Leu	missense	Exon 13 of 13	ENSP00000394770.2
	CMYA5	ENST00000506603.5	TSL:1	n.3916C>T		non_coding_transcript_exon	Exon 11 of 11
	CMYA5	ENST00000940891.1		c.2075C>T	p.Pro692Leu	missense	Exon 13 of 13	ENSP00000610950.1

Frequencies

GnomAD3 genomes AF: 0.0815 AC: 12390 AN: 152074 Hom.: 663 Cov.: 32

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0789

Gnomad ASJ AF: 0.0946

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0620

Gnomad FIN AF: 0.0897

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.0910

GnomAD2 exomes AF: 0.0866 AC: 21320 AN: 246112 AF XY: 0.0901

Gnomad AFR exome AF: 0.0188

Gnomad AMR exome AF: 0.0504

Gnomad ASJ exome AF: 0.0916

Gnomad EAS exome AF: 0.000281

Gnomad FIN exome AF: 0.0892

Gnomad NFE exome AF: 0.126

Gnomad OTH exome AF: 0.0853

GnomAD4 exome AF: 0.108 AC: 157848 AN: 1460156 Hom.: 9340 Cov.: 32 AF XY: 0.108 AC XY: 78179 AN XY: 726164

African (AFR) AF: 0.0175 AC: 586 AN: 33464

American (AMR) AF: 0.0532 AC: 2370 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.0977 AC: 2550 AN: 26088

East Asian (EAS) AF: 0.000328 AC: 13 AN: 39664

South Asian (SAS) AF: 0.0653 AC: 5617 AN: 85982

European-Finnish (FIN) AF: 0.0898 AC: 4789 AN: 53324

Middle Eastern (MID) AF: 0.0898 AC: 518 AN: 5766

European-Non Finnish (NFE) AF: 0.122 AC: 135459 AN: 1110998

Other (OTH) AF: 0.0986 AC: 5946 AN: 60310

GnomAD4 genome AF: 0.0814 AC: 12387 AN: 152192 Hom.: 664 Cov.: 32 AF XY: 0.0778 AC XY: 5790 AN XY: 74396

African (AFR) AF: 0.0214 AC: 890 AN: 41536

American (AMR) AF: 0.0790 AC: 1208 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0946 AC: 328 AN: 3468

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5166

South Asian (SAS) AF: 0.0617 AC: 297 AN: 4816

European-Finnish (FIN) AF: 0.0897 AC: 951 AN: 10604

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8432 AN: 67996

Other (OTH) AF: 0.0891 AC: 188 AN: 2110

Alfa AF: 0.109 Hom.: 3713

Bravo AF: 0.0769

TwinsUK AF: 0.119 AC: 441

ALSPAC AF: 0.117 AC: 452

ESP6500AA AF: 0.0254 AC: 94

ESP6500EA AF: 0.119 AC: 978

ExAC AF: 0.0881 AC: 10641

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.13	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		6.8
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0090	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.30
MPC		0.36
ClinPred		0.066	T
GERP RS		6.0
Varity_R		0.31
gMVP		0.80
Mutation Taster		=59/41	polymorphism (auto)

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: rs10043986; hg19: chr5-79095417; COSMIC: COSV69745360;