NM_153610.5:c.103G>A

Variant names:

• chr5-79690010-G-A
• rs141830505
• NM_153610.5:c.103G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153610.5(CMYA5):​c.103G>A​(p.Glu35Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,484,580 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (71 hom.)
• Consequence: CMYA5 NM_153610.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.33
• Publications: 4 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004689783).
• BP6: Variant 5-79690010-G-A is Benign according to our data. Variant chr5-79690010-G-A is described in ClinVar as Benign. ClinVar VariationId is 791626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0541 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.103G>A	p.Glu35Lys	missense	Exon 1 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.103G>A	p.Glu35Lys	missense	Exon 1 of 13	ENSP00000394770.2	Q8N3K9
	CMYA5	ENST00000940891.1		c.103G>A	p.Glu35Lys	missense	Exon 1 of 13	ENSP00000610950.1
	CMYA5	ENST00000856934.1		c.103G>A	p.Glu35Lys	missense	Exon 1 of 13	ENSP00000526993.1

Frequencies

GnomAD3 genomes AF: 0.00306 AC: 466 AN: 152230 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0477

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00301

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00170

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00401 AC: 391 AN: 97422 AF XY: 0.00374

Gnomad AFR exome AF: 0.000317

Gnomad AMR exome AF: 0.00118

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0443

Gnomad FIN exome AF: 0.00292

Gnomad NFE exome AF: 0.00179

Gnomad OTH exome AF: 0.00296

GnomAD4 exome AF: 0.00303 AC: 4037 AN: 1332232 Hom.: 71 Cov.: 26 AF XY: 0.00295 AC XY: 1937 AN XY: 655614

African (AFR) AF: 0.000406 AC: 11 AN: 27090

American (AMR) AF: 0.00138 AC: 42 AN: 30362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22234

East Asian (EAS) AF: 0.0563 AC: 1728 AN: 30698

South Asian (SAS) AF: 0.00208 AC: 153 AN: 73662

European-Finnish (FIN) AF: 0.00321 AC: 153 AN: 47628

Middle Eastern (MID) AF: 0.000637 AC: 3 AN: 4706

European-Non Finnish (NFE) AF: 0.00173 AC: 1804 AN: 1040710

Other (OTH) AF: 0.00259 AC: 143 AN: 55142

GnomAD4 genome AF: 0.00306 AC: 466 AN: 152348 Hom.: 11 Cov.: 32 AF XY: 0.00357 AC XY: 266 AN XY: 74496

African (AFR) AF: 0.000553 AC: 23 AN: 41590

American (AMR) AF: 0.00176 AC: 27 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0478 AC: 247 AN: 5168

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4826

European-Finnish (FIN) AF: 0.00301 AC: 32 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00170 AC: 116 AN: 68036

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00243 Hom.: 1

Bravo AF: 0.00361

ESP6500AA AF: 0.000288 AC: 1

ESP6500EA AF: 0.00130 AC: 9

ExAC AF: 0.00200 AC: 91

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Benign	0.074
Eigen_PC	Benign	0.053
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.3
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.070
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.054	T
Polyphen		0.98	D
Vest4		0.26
MVP		0.34
MPC		0.24
ClinPred		0.033	T
GERP RS		3.2
PromoterAI		0.065	Neutral
Varity_R		0.31
gMVP		0.12
Mutation Taster		=95/5	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: rs141830505; hg19: chr5-78985833; COSMIC: COSV99706307; COSMIC: COSV99706307;