NM_006457.5:c.1141A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006457.5(PDLIM5):​c.1141A>G​(p.Thr381Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 1,606,886 control chromosomes in the GnomAD database, including 147,689 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 11293 hom., cov: 32)
Exomes 𝑓: 0.43 ( 136396 hom. )

Consequence

PDLIM5
NM_006457.5 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.44

Publications

51 publications found
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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=1.2841005E-5).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PDLIM5NM_006457.5 linkc.1141A>G p.Thr381Ala missense_variant Exon 9 of 13 ENST00000317968.9 NP_006448.5 Q96HC4-1A0A024RDE8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PDLIM5ENST00000317968.9 linkc.1141A>G p.Thr381Ala missense_variant Exon 9 of 13 1 NM_006457.5 ENSP00000321746.4 Q96HC4-1

Frequencies

GnomAD3 genomes
AF:
0.367
AC:
55796
AN:
151892
Hom.:
11291
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.188
Gnomad AMI
AF:
0.493
Gnomad AMR
AF:
0.391
Gnomad ASJ
AF:
0.504
Gnomad EAS
AF:
0.404
Gnomad SAS
AF:
0.623
Gnomad FIN
AF:
0.495
Gnomad MID
AF:
0.547
Gnomad NFE
AF:
0.421
Gnomad OTH
AF:
0.374
GnomAD2 exomes
AF:
0.439
AC:
110030
AN:
250360
AF XY:
0.453
show subpopulations
Gnomad AFR exome
AF:
0.180
Gnomad AMR exome
AF:
0.425
Gnomad ASJ exome
AF:
0.504
Gnomad EAS exome
AF:
0.398
Gnomad FIN exome
AF:
0.495
Gnomad NFE exome
AF:
0.424
Gnomad OTH exome
AF:
0.453
GnomAD4 exome
AF:
0.427
AC:
621113
AN:
1454878
Hom.:
136396
Cov.:
30
AF XY:
0.435
AC XY:
315009
AN XY:
724146
show subpopulations
African (AFR)
AF:
0.180
AC:
6001
AN:
33358
American (AMR)
AF:
0.418
AC:
18627
AN:
44576
Ashkenazi Jewish (ASJ)
AF:
0.502
AC:
13082
AN:
26054
East Asian (EAS)
AF:
0.402
AC:
15934
AN:
39640
South Asian (SAS)
AF:
0.610
AC:
52417
AN:
85950
European-Finnish (FIN)
AF:
0.490
AC:
26154
AN:
53388
Middle Eastern (MID)
AF:
0.498
AC:
2865
AN:
5758
European-Non Finnish (NFE)
AF:
0.416
AC:
460226
AN:
1106036
Other (OTH)
AF:
0.429
AC:
25807
AN:
60118
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.476
Heterozygous variant carriers
0
15438
30877
46315
61754
77192
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
14068
28136
42204
56272
70340
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.367
AC:
55810
AN:
152008
Hom.:
11293
Cov.:
32
AF XY:
0.375
AC XY:
27888
AN XY:
74294
show subpopulations
African (AFR)
AF:
0.188
AC:
7791
AN:
41474
American (AMR)
AF:
0.391
AC:
5961
AN:
15258
Ashkenazi Jewish (ASJ)
AF:
0.504
AC:
1748
AN:
3470
East Asian (EAS)
AF:
0.405
AC:
2088
AN:
5156
South Asian (SAS)
AF:
0.620
AC:
2988
AN:
4818
European-Finnish (FIN)
AF:
0.495
AC:
5225
AN:
10564
Middle Eastern (MID)
AF:
0.537
AC:
158
AN:
294
European-Non Finnish (NFE)
AF:
0.421
AC:
28599
AN:
67950
Other (OTH)
AF:
0.380
AC:
803
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1716
3431
5147
6862
8578
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
552
1104
1656
2208
2760
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.408
Hom.:
49181
Bravo
AF:
0.350
TwinsUK
AF:
0.418
AC:
1550
ALSPAC
AF:
0.412
AC:
1588
ESP6500AA
AF:
0.186
AC:
821
ESP6500EA
AF:
0.422
AC:
3630
ExAC
AF:
0.435
AC:
52807
Asia WGS
AF:
0.503
AC:
1745
AN:
3478
EpiCase
AF:
0.428
EpiControl
AF:
0.438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.055
BayesDel_addAF
Benign
-0.69
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
0.0030
DANN
Benign
0.24
DEOGEN2
Benign
0.0079
T;.;T;.;.;.
Eigen
Benign
-2.1
Eigen_PC
Benign
-2.2
FATHMM_MKL
Benign
0.0043
N
LIST_S2
Benign
0.10
T;T;T;T;T;.
MetaRNN
Benign
0.000013
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.81
.;.;L;.;.;.
PhyloP100
-1.4
PrimateAI
Benign
0.26
T
PROVEAN
Benign
0.26
.;.;N;N;.;N
REVEL
Benign
0.023
Sift
Benign
1.0
.;.;T;T;.;T
Sift4G
Benign
0.89
T;T;T;T;T;T
Polyphen
0.0
.;.;B;.;B;.
Vest4
0.032
MPC
0.10
ClinPred
0.018
T
GERP RS
-11
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.068
gMVP
0.26
Mutation Taster
=96/4
polymorphism (auto)

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

Other links and lift over

dbSNP: rs7690296; hg19: chr4-95561459; COSMIC: COSV58745700; API