5-79729249-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.484C>T​(p.Pro162Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000034 ( 0 hom. )

Consequence

CMYA5
NM_153610.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.93
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=0.1400232).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CMYA5NM_153610.5 linkuse as main transcriptc.484C>T p.Pro162Ser missense_variant 2/13 ENST00000446378.3
CMYA5XM_047416911.1 linkuse as main transcriptc.484C>T p.Pro162Ser missense_variant 2/6
CMYA5XR_001742036.3 linkuse as main transcriptn.556C>T non_coding_transcript_exon_variant 2/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CMYA5ENST00000446378.3 linkuse as main transcriptc.484C>T p.Pro162Ser missense_variant 2/135 NM_153610.5 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000122
AC:
3
AN:
245376
Hom.:
0
AF XY:
0.0000150
AC XY:
2
AN XY:
133122
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:
0.000101
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000343
AC:
5
AN:
1458296
Hom.:
0
Cov.:
34
AF XY:
0.00000414
AC XY:
3
AN XY:
725414
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:
0.0000585
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
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 23, 2024The c.484C>T (p.P162S) 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 484, causing the proline (P) at amino acid position 162 to be replaced by a serine (S). 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
0.13
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.034
T
Eigen
Benign
0.021
Eigen_PC
Benign
0.081
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.0083
T
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
0.99
N
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-3.6
D
REVEL
Benign
0.053
Sift
Benign
0.089
T
Sift4G
Benign
0.44
T
Polyphen
0.80
P
Vest4
0.18
MutPred
0.22
Gain of phosphorylation at P162 (P = 0.022);
MVP
0.42
MPC
0.056
ClinPred
0.61
D
GERP RS
4.8
Varity_R
0.12
gMVP
0.26

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: rs781301181; hg19: chr5-79025072; API