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. 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMYA5	NM_153610.5	c.10074C>G	p.His3358Gln	missense_variant	Exon 2 of 13	ENST00000446378.3	NP_705838.3
CMYA5	XM_047416911.1	c.10074C>G	p.His3358Gln	missense_variant	Exon 2 of 6		XP_047272867.1
CMYA5	XR_001742036.3	n.10146C>G		non_coding_transcript_exon_variant	Exon 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMYA5	ENST00000446378.3	c.10074C>G	p.His3358Gln	missense_variant	Exon 2 of 13	5	NM_153610.5	ENSP00000394770.2
CMYA5	ENST00000506603.5	n.698C>G		non_coding_transcript_exon_variant	Exon 1 of 11	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 v4.3

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;