Variant 5-79729177-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_153610.5(CMYA5):c.412T>C(p.Ser138Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,596 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CMYA5
NM_153610.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.12

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 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=0.17925742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CMYA5	NM_153610.5 linkuse as main transcript	c.412T>C	p.Ser138Pro	missense_variant	2/13	ENST00000446378.3
CMYA5	XM_047416911.1 linkuse as main transcript	c.412T>C	p.Ser138Pro	missense_variant	2/6
CMYA5	XR_001742036.3 linkuse as main transcript	n.484T>C		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CMYA5	ENST00000446378.3 linkuse as main transcript	c.412T>C	p.Ser138Pro	missense_variant	2/13	5	NM_153610.5	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460596

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726518

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Apr 19, 2023

The c.412T>C (p.S138P) alteration is located in exon 2 (coding exon 2) of the CMYA5 gene. This alteration results from a T to C substitution at nucleotide position 412, causing the serine (S) at amino acid position 138 to be replaced by a proline (P). 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

0.15

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.036

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.65

M_CAP

Benign

0.047

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.99

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.18

Sift

Uncertain

0.028

Sift4G

Uncertain

0.0040

Polyphen

0.80

Vest4

0.31

MutPred

0.15

Gain of relative solvent accessibility (P = 0.0027);

MVP

0.50

MPC

0.26

ClinPred

0.87

GERP RS

4.2

Varity_R

0.37

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over