5-79729290-G-T

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

1
17

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]

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 UniProt
CMYA5NM_153610.5 linkuse as main transcriptc.525G>T p.Gln175His missense_variant 2/13 ENST00000446378.3 NP_705838.3
CMYA5XM_047416911.1 linkuse as main transcriptc.525G>T p.Gln175His missense_variant 2/6 XP_047272867.1
CMYA5XR_001742036.3 linkuse as main transcriptn.597G>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.525G>T p.Gln175His missense_variant 2/135 NM_153610.5 ENSP00000394770 P1

Frequencies

GnomAD3 genomes
AF:
0.00615
AC:
936
AN:
152150
Hom.:
8
Cov.:
32
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.:
2
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.:
9
Cov.:
34
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.:
8
Cov.:
32
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.:
6
Bravo
AF:
0.00698
ESP6500AA
AF:
0.0232
AC:
86
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00221
AC:
267
Asia WGS
AF:
0.000866
AC:
3
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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
14
DANN
Benign
0.86
DEOGEN2
Benign
0.018
T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.59
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.51
T
MetaRNN
Benign
0.0027
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.060
Sift
Uncertain
0.010
D
Sift4G
Benign
0.14
T
Polyphen
0.94
P
Vest4
0.12
MutPred
0.11
Loss of sheet (P = 0.1158);
MVP
0.20
MPC
0.062
ClinPred
0.021
T
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.

Other links and lift over

dbSNP: rs6895605; hg19: chr5-79025113; COSMIC: COSV99069768; API