Variant chr5-79729290-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_153610.5(CMYA5):c.525G>T(p.Gln175His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,610,588 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0061 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00063 ( 9 hom. )

Consequence

CMYA5
NM_153610.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.411

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026955307).

BP6

Variant 5-79729290-G-T is Benign according to our data. Variant chr5-79729290-G-T is described in ClinVar as [Benign]. Clinvar id is 733687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00615 (936/152268) while in subpopulation AFR AF= 0.0216 (898/41554). AF 95% confidence interval is 0.0204. There are 8 homozygotes in gnomad4. There are 440 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CMYA5	NM_153610.5 linkuse as main transcript	c.525G>T	p.Gln175His	missense_variant	2/13	ENST00000446378.3	NP_705838.3
CMYA5	XM_047416911.1 linkuse as main transcript	c.525G>T	p.Gln175His	missense_variant	2/6		XP_047272867.1
CMYA5	XR_001742036.3 linkuse as main transcript	n.597G>T		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMYA5	ENST00000446378.3 linkuse as main transcript	c.525G>T	p.Gln175His	missense_variant	2/13	5	NM_153610.5	ENSP00000394770	P1

Frequencies

GnomAD3 genomes

AF:

0.00615

AC:

936

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

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:

0.00669

GnomAD3 exomes

AF:

0.00176

AC:

431

AN:

245068

Hom.:

AF XY:

0.00129

AC XY:

172

AN XY:

132906

show subpopulations

Gnomad AFR exome

AF:

0.0250

Gnomad AMR exome

AF:

0.00107

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:

0.00000897

Gnomad OTH exome

AF:

0.00101

GnomAD4 exome

AF:

0.000634

AC:

924

AN:

1458320

Hom.:

Cov.:

AF XY:

0.000531

AC XY:

385

AN XY:

725410

show subpopulations

Gnomad4 AFR exome

AF:

0.0241

Gnomad4 AMR exome

AF:

0.000935

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000586

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.00116

GnomAD4 genome

AF:

0.00615

AC:

936

AN:

152268

Hom.:

Cov.:

AF XY:

0.00591

AC XY:

440

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0216

Gnomad4 AMR

AF:

0.00150

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:

0.00662

Alfa

AF:

0.00138

Hom.:

Bravo

AF:

0.00698

ESP6500AA

AF:

0.0232

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00221

AC:

267

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.018

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.7

REVEL

Benign

0.060

Sift

Uncertain

0.010

Sift4G

Benign

0.14

Polyphen

0.94

Vest4

0.12

MutPred

0.11

Loss of sheet (P = 0.1158);

MVP

0.20

MPC

0.062

ClinPred

0.021

GERP RS

1.5

Varity_R

0.071

gMVP

0.22

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over