chr4-94575789-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2
The NM_006457.5(PDLIM5):c.465G>A(p.Ala155=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,613,928 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0089 ( 13 hom., cov: 32)
Exomes 𝑓: 0.015 ( 249 hom. )
Consequence
PDLIM5
NM_006457.5 synonymous
NM_006457.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.910
Genes affected
PDLIM5 (HGNC:17468): (PDZ and LIM domain 5) This gene encodes a member of a family of proteins that possess a 100-amino acid PDZ domain at the N terminus and one to three LIM domains at the C-terminus. This family member functions as a scaffold protein that tethers protein kinases to the Z-disk in striated muscles. It is thought to function in cardiomyocyte expansion and in restraining postsynaptic growth of excitatory synapses. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
?
Variant 4-94575789-G-A is Benign according to our data. Variant chr4-94575789-G-A is described in ClinVar as [Benign]. Clinvar id is 777394.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.91 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00894 (1359/152078) while in subpopulation NFE AF= 0.0161 (1092/67986). AF 95% confidence interval is 0.0153. There are 13 homozygotes in gnomad4. There are 590 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1358 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDLIM5 | NM_006457.5 | c.465G>A | p.Ala155= | synonymous_variant | 5/13 | ENST00000317968.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDLIM5 | ENST00000317968.9 | c.465G>A | p.Ala155= | synonymous_variant | 5/13 | 1 | NM_006457.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00894 AC: 1358AN: 151960Hom.: 13 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
1358
AN:
151960
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00880 AC: 2211AN: 251296Hom.: 19 AF XY: 0.00895 AC XY: 1215AN XY: 135818
GnomAD3 exomes
AF:
AC:
2211
AN:
251296
Hom.:
AF XY:
AC XY:
1215
AN XY:
135818
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0155 AC: 22625AN: 1461850Hom.: 249 Cov.: 33 AF XY: 0.0151 AC XY: 10980AN XY: 727232
GnomAD4 exome
AF:
AC:
22625
AN:
1461850
Hom.:
Cov.:
33
AF XY:
AC XY:
10980
AN XY:
727232
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00894 AC: 1359AN: 152078Hom.: 13 Cov.: 32 AF XY: 0.00794 AC XY: 590AN XY: 74342
GnomAD4 genome
?
AF:
AC:
1359
AN:
152078
Hom.:
Cov.:
32
AF XY:
AC XY:
590
AN XY:
74342
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
5
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 11, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at