5-79729287-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153610.5(CMYA5):ā€‹c.522C>Gā€‹(p.Ser174Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,610,858 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.000016 ( 0 hom. )

Consequence

CMYA5
NM_153610.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0960
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.022503585).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CMYA5NM_153610.5 linkuse as main transcriptc.522C>G p.Ser174Arg missense_variant 2/13 ENST00000446378.3 NP_705838.3
CMYA5XM_047416911.1 linkuse as main transcriptc.522C>G p.Ser174Arg missense_variant 2/6 XP_047272867.1
CMYA5XR_001742036.3 linkuse as main transcriptn.594C>G non_coding_transcript_exon_variant 2/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CMYA5ENST00000446378.3 linkuse as main transcriptc.522C>G p.Ser174Arg missense_variant 2/135 NM_153610.5 ENSP00000394770 P1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152156
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000770
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000611
AC:
15
AN:
245390
Hom.:
0
AF XY:
0.0000376
AC XY:
5
AN XY:
133080
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000791
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000896
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000158
AC:
23
AN:
1458586
Hom.:
0
Cov.:
34
AF XY:
0.0000124
AC XY:
9
AN XY:
725526
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000529
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152272
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000772
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.0000497
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 05, 2024The c.522C>G (p.S174R) alteration is located in exon 2 (coding exon 2) of the CMYA5 gene. This alteration results from a C to G substitution at nucleotide position 522, causing the serine (S) at amino acid position 174 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.021
T
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.51
FATHMM_MKL
Benign
0.047
N
LIST_S2
Benign
0.61
T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.023
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.32
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.073
Sift
Uncertain
0.0040
D
Sift4G
Benign
0.18
T
Polyphen
0.95
P
Vest4
0.20
MutPred
0.29
Gain of solvent accessibility (P = 7e-04);
MVP
0.26
MPC
0.28
ClinPred
0.18
T
GERP RS
-0.51
Varity_R
0.15
gMVP
0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs186943498; hg19: chr5-79025110; API