dbSNP rs1211931518: CMYA5:p.Gly34Ser (chr5-79690007-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153610.5(CMYA5):c.100G>A(p.Gly34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000188 in 1,327,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

CMYA5
NM_153610.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47

Publications

0 publications found

Variant links:

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]

CMYA5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.116958946).

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.100G>A	p.Gly34Ser	missense	Exon 1 of 13	NP_705838.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CMYA5	ENST00000446378.3	TSL:5 MANE Select	c.100G>A	p.Gly34Ser	missense	Exon 1 of 13	ENSP00000394770.2	Q8N3K9
CMYA5	ENST00000940891.1		c.100G>A	p.Gly34Ser	missense	Exon 1 of 13	ENSP00000610950.1
CMYA5	ENST00000856934.1		c.100G>A	p.Gly34Ser	missense	Exon 1 of 13	ENSP00000526993.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000197

AC:

AN:

101406

AF XY:

0.0000184

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000105

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000188

AC:

AN:

1327940

Hom.:

Cov.:

AF XY:

0.0000183

AC XY:

AN XY:

654492

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27024

American (AMR)

AF:

0.000163

AC:

AN:

30748

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22478

East Asian (EAS)

AF:

0.00

AC:

AN:

30784

South Asian (SAS)

AF:

0.00

AC:

AN:

74256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47838

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4668

European-Non Finnish (NFE)

AF:

0.0000184

AC:

AN:

1035142

Other (OTH)

AF:

0.0000182

AC:

AN:

55002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.019

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.47

M_CAP

Benign

0.056

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

2.5

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.7

REVEL

Benign

0.090

Sift

Uncertain

0.0080

Sift4G

Benign

0.094

Polyphen

0.80

Vest4

0.15

MutPred

0.25

Gain of phosphorylation at G34 (P = 2e-04)

MVP

0.18

MPC

0.057

ClinPred

0.16

GERP RS

2.8

PromoterAI

0.040

Neutral

(source)

Varity_R

0.17

gMVP

0.038

Mutation Taster

=98/2

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over