5-79728971-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_153610.5(CMYA5):​c.206C>T​(p.Pro69Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CMYA5
NM_153610.5 missense

Scores

7
7
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.11
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.819

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CMYA5NM_153610.5 linkuse as main transcriptc.206C>T p.Pro69Leu missense_variant 2/13 ENST00000446378.3 NP_705838.3
CMYA5XM_047416911.1 linkuse as main transcriptc.206C>T p.Pro69Leu missense_variant 2/6 XP_047272867.1
CMYA5XR_001742036.3 linkuse as main transcriptn.278C>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.206C>T p.Pro69Leu missense_variant 2/135 NM_153610.5 ENSP00000394770 P1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152024
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248938
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135048
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000886
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461080
Hom.:
0
Cov.:
33
AF XY:
0.00000550
AC XY:
4
AN XY:
726824
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152024
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74254
show subpopulations
Gnomad4 AFR
AF:
0.0000242
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000370
Hom.:
0
ExAC
AF:
0.00000828
AC:
1

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 GeneticsApr 06, 2023The c.206C>T (p.P69L) 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 206, causing the proline (P) at amino acid position 69 to be replaced by a leucine (L). 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
0.43
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.18
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.057
T
Eigen
Pathogenic
0.75
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.059
D
MetaRNN
Pathogenic
0.82
D
MetaSVM
Benign
-0.47
T
MutationAssessor
Benign
1.5
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.65
T
PROVEAN
Pathogenic
-6.2
D
REVEL
Uncertain
0.52
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0060
D
Polyphen
1.0
D
Vest4
0.77
MVP
0.71
MPC
0.32
ClinPred
0.98
D
GERP RS
5.8
Varity_R
0.49
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs747442785; hg19: chr5-79024794; API