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GeneBe

4-94575789-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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.910
Variant links:
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
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.91 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1358 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDLIM5NM_006457.5 linkuse as main transcriptc.465G>A p.Ala155= synonymous_variant 5/13 ENST00000317968.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDLIM5ENST00000317968.9 linkuse as main transcriptc.465G>A p.Ala155= synonymous_variant 5/131 NM_006457.5 P3Q96HC4-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00894
AC:
1358
AN:
151960
Hom.:
13
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00305
Gnomad AMI
AF:
0.00219
Gnomad AMR
AF:
0.00485
Gnomad ASJ
AF:
0.00259
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00394
Gnomad FIN
AF:
0.00170
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0160
Gnomad OTH
AF:
0.00913
GnomAD3 exomes
AF:
0.00880
AC:
2211
AN:
251296
Hom.:
19
AF XY:
0.00895
AC XY:
1215
AN XY:
135818
show subpopulations
Gnomad AFR exome
AF:
0.00326
Gnomad AMR exome
AF:
0.00344
Gnomad ASJ exome
AF:
0.00337
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00343
Gnomad FIN exome
AF:
0.00375
Gnomad NFE exome
AF:
0.0156
Gnomad OTH exome
AF:
0.00766
GnomAD4 exome
AF:
0.0155
AC:
22625
AN:
1461850
Hom.:
249
Cov.:
33
AF XY:
0.0151
AC XY:
10980
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00278
Gnomad4 AMR exome
AF:
0.00335
Gnomad4 ASJ exome
AF:
0.00298
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00388
Gnomad4 FIN exome
AF:
0.00348
Gnomad4 NFE exome
AF:
0.0188
Gnomad4 OTH exome
AF:
0.0134
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00894
AC:
1359
AN:
152078
Hom.:
13
Cov.:
32
AF XY:
0.00794
AC XY:
590
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00301
Gnomad4 AMR
AF:
0.00484
Gnomad4 ASJ
AF:
0.00259
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00415
Gnomad4 FIN
AF:
0.00170
Gnomad4 NFE
AF:
0.0161
Gnomad4 OTH
AF:
0.00903
Alfa
AF:
0.0128
Hom.:
7
Bravo
AF:
0.00962
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.0167
EpiControl
AF:
0.0158

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 submitterclinical testingInvitaeJul 11, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.28
Cadd
Benign
13
Dann
Benign
0.70

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: rs115743950; hg19: chr4-95496940; COSMIC: COSV58747792; COSMIC: COSV58747792; API