Variant 4-94640308-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000317968.9(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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

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

Exomes 𝑓: 0.43 ( 136396 hom. )

Consequence

PDLIM5
ENST00000317968.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.44

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]

PDLIM5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PDLIM5	NM_006457.5 linkuse as main transcript	c.1141A>G	p.Thr381Ala	missense_variant	9/13	ENST00000317968.9	NP_006448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDLIM5	ENST00000317968.9 linkuse as main transcript	c.1141A>G	p.Thr381Ala	missense_variant	9/13	1	NM_006457.5	ENSP00000321746	P3	Q96HC4-1

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

55796

AN:

151892

Hom.:

11291

Cov.:

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

GnomAD3 exomes

AF:

0.439

AC:

110030

AN:

250360

Hom.:

25350

AF XY:

0.453

AC XY:

61284

AN XY:

135306

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 SAS exome

AF:

0.613

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.:

AF XY:

0.435

AC XY:

315009

AN XY:

724146

show subpopulations

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.418

Gnomad4 ASJ exome

AF:

0.502

Gnomad4 EAS exome

AF:

0.402

Gnomad4 SAS exome

AF:

0.610

Gnomad4 FIN exome

AF:

0.490

Gnomad4 NFE exome

AF:

0.416

Gnomad4 OTH exome

AF:

0.429

GnomAD4 genome

AF:

0.367

AC:

55810

AN:

152008

Hom.:

11293

Cov.:

AF XY:

0.375

AC XY:

27888

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.188

Gnomad4 AMR

AF:

0.391

Gnomad4 ASJ

AF:

0.504

Gnomad4 EAS

AF:

0.405

Gnomad4 SAS

AF:

0.620

Gnomad4 FIN

AF:

0.495

Gnomad4 NFE

AF:

0.421

Gnomad4 OTH

AF:

0.380

Alfa

AF:

0.417

Hom.:

34985

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

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

LIST_S2

Benign

0.10

T;T;T;T;T;.

MetaRNN

Benign

0.000013

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

.;.;L;.;.;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.26

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

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.068

gMVP

0.26

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over