5-79738839-C-G

Variant names:

• chr5-79738839-C-G
• rs3828611
• NM_153610.5:c.10074C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153610.5(CMYA5):​c.10074C>G​(p.His3358Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0875 in 1,613,660 control chromosomes in the GnomAD database, including 10,935 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. H3358H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.13 (1904 hom., cov: 32)
  • Exomes 𝑓: 0.084 (9031 hom.)
• Consequence: CMYA5 NM_153610.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003689319).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 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.10074C>G	p.His3358Gln	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.10074C>G	p.His3358Gln	missense	Exon 2 of 13	ENSP00000394770.2
	CMYA5	ENST00000506603.5	TSL:1	n.698C>G		non_coding_transcript_exon	Exon 1 of 11
	CMYA5	ENST00000940891.1		c.526-4988C>G		intron	N/A	ENSP00000610950.1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18996 AN: 151966 Hom.: 1887 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0552

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.0914

Gnomad FIN AF: 0.0977

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0661

Gnomad OTH AF: 0.0955

GnomAD2 exomes AF: 0.104 AC: 25806 AN: 248930 AF XY: 0.0991

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.0360

Gnomad ASJ exome AF: 0.0520

Gnomad EAS exome AF: 0.410

Gnomad FIN exome AF: 0.0989

Gnomad NFE exome AF: 0.0667

Gnomad OTH exome AF: 0.0767

GnomAD4 exome AF: 0.0836 AC: 122158 AN: 1461576 Hom.: 9031 Cov.: 35 AF XY: 0.0830 AC XY: 60346 AN XY: 727062

African (AFR) AF: 0.245 AC: 8211 AN: 33468

American (AMR) AF: 0.0383 AC: 1712 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.0550 AC: 1436 AN: 26128

East Asian (EAS) AF: 0.465 AC: 18447 AN: 39692

South Asian (SAS) AF: 0.0932 AC: 8039 AN: 86252

European-Finnish (FIN) AF: 0.0985 AC: 5260 AN: 53394

Middle Eastern (MID) AF: 0.0363 AC: 209 AN: 5762

European-Non Finnish (NFE) AF: 0.0659 AC: 73282 AN: 1111810

Other (OTH) AF: 0.0921 AC: 5562 AN: 60374

GnomAD4 genome AF: 0.125 AC: 19059 AN: 152084 Hom.: 1904 Cov.: 32 AF XY: 0.128 AC XY: 9551 AN XY: 74340

African (AFR) AF: 0.235 AC: 9748 AN: 41476

American (AMR) AF: 0.0550 AC: 839 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 197 AN: 3470

East Asian (EAS) AF: 0.405 AC: 2094 AN: 5170

South Asian (SAS) AF: 0.0914 AC: 440 AN: 4812

European-Finnish (FIN) AF: 0.0977 AC: 1033 AN: 10574

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0661 AC: 4492 AN: 68002

Other (OTH) AF: 0.0945 AC: 199 AN: 2106

Alfa AF: 0.0726 Hom.: 564

Bravo AF: 0.129

TwinsUK AF: 0.0696 AC: 258

ALSPAC AF: 0.0654 AC: 252

ESP6500AA AF: 0.225 AC: 933

ESP6500EA AF: 0.0658 AC: 555

ExAC AF: 0.107 AC: 12994

EpiCase AF: 0.0609

EpiControl AF: 0.0563

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.26
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00092	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.5	N
PhyloP100		0.10
PrimateAI	Benign	0.24	T
PROVEAN	Benign	2.6	N
REVEL	Benign	0.040
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.027
MutPred		0.16		Loss of glycosylation at S3357 (P = 0.1338)
MPC		0.055
ClinPred		0.000019	T
GERP RS		2.2
Varity_R		0.026
gMVP		0.098
Mutation Taster		=96/4	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: rs3828611; hg19: chr5-79034662; COSMIC: COSV71405666;