5-79729090-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153610.5(CMYA5):​c.325C>T​(p.Arg109Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,613,438 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000051 ( 1 hom. )

Consequence

CMYA5
NM_153610.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0240
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.098446935).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CMYA5NM_153610.5 linkuse as main transcriptc.325C>T p.Arg109Trp missense_variant 2/13 ENST00000446378.3 NP_705838.3
CMYA5XM_047416911.1 linkuse as main transcriptc.325C>T p.Arg109Trp missense_variant 2/6 XP_047272867.1
CMYA5XR_001742036.3 linkuse as main transcriptn.397C>T 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.325C>T p.Arg109Trp missense_variant 2/135 NM_153610.5 ENSP00000394770 P1

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
151958
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000726
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000683
AC:
17
AN:
248820
Hom.:
1
AF XY:
0.0000815
AC XY:
11
AN XY:
134992
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000532
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000513
AC:
75
AN:
1461480
Hom.:
1
Cov.:
33
AF XY:
0.0000605
AC XY:
44
AN XY:
727008
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000448
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000278
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000378
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000395
AC:
6
AN:
151958
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74208
show subpopulations
Gnomad4 AFR
AF:
0.0000726
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000529
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000122
AC:
1
ExAC
AF:
0.0000828
AC:
10
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 GeneticsNov 08, 2022The c.325C>T (p.R109W) alteration is located in exon 2 (coding exon 2) of the CMYA5 gene. This alteration results from a C to T substitution at nucleotide position 325, causing the arginine (R) at amino acid position 109 to be replaced by a tryptophan (W). 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
Benign
0.099
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.020
T
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.091
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.098
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.75
N
REVEL
Benign
0.073
Sift
Uncertain
0.013
D
Sift4G
Uncertain
0.032
D
Polyphen
0.88
P
Vest4
0.20
MVP
0.45
MPC
0.065
ClinPred
0.11
T
GERP RS
2.7
Varity_R
0.069
gMVP
0.11

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: rs376295720; hg19: chr5-79024913; API