rs112661328

Positions:

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_014476.6(PDLIM3):c.162C>T(p.Gly54=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00994 in 1,614,126 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 7 hom., cov: 33)

Exomes 𝑓: 0.010 ( 99 hom. )

Consequence

PDLIM3
NM_014476.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.74

Variant links:

Genes affected

PDLIM3 (HGNC:20767): (PDZ and LIM domain 3) The protein encoded by this gene contains a PDZ domain and a LIM domain, indicating that it may be involved in cytoskeletal assembly. In support of this, the encoded protein has been shown to bind the spectrin-like repeats of alpha-actinin-2 and to colocalize with alpha-actinin-2 at the Z lines of skeletal muscle. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. Aberrant alternative splicing of this gene may play a role in myotonic dystrophy. [provided by RefSeq, Apr 2012]

PDLIM3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 4-185525103-G-A is Benign according to our data. Variant chr4-185525103-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 138668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-185525103-G-A is described in Lovd as [Benign]. Variant chr4-185525103-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.74 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDLIM3	NM_014476.6 linkuse as main transcript	c.162C>T	p.Gly54=	synonymous_variant	2/8	ENST00000284767.12	NP_055291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDLIM3	ENST00000284767.12 linkuse as main transcript	c.162C>T	p.Gly54=	synonymous_variant	2/8	5	NM_014476.6	ENSP00000284767	A1	Q53GG5-1

Frequencies

GnomAD3 genomes

AF:

0.00707

AC:

1076

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0119

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.00799

AC:

2008

AN:

251356

Hom.:

AF XY:

0.00783

AC XY:

1064

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00234

Gnomad AMR exome

AF:

0.00489

Gnomad ASJ exome

AF:

0.00784

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00287

Gnomad FIN exome

AF:

0.0157

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.0102

AC:

14971

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00986

AC XY:

7167

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.00505

Gnomad4 ASJ exome

AF:

0.00800

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.00315

Gnomad4 FIN exome

AF:

0.0166

Gnomad4 NFE exome

AF:

0.0115

Gnomad4 OTH exome

AF:

0.00853

GnomAD4 genome

AF:

0.00707

AC:

1077

AN:

152322

Hom.:

Cov.:

AF XY:

0.00709

AC XY:

528

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00233

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0119

Gnomad4 NFE

AF:

0.0106

Gnomad4 OTH

AF:

0.00945

Alfa

AF:

0.00901

Hom.:

Bravo

AF:

0.00667

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00911

EpiControl

AF:

0.00954

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Gly54Gly in exon 2 of PDLIM3: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 1.0% (85/8600) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs112661328). -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 11, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	May 17, 2022	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 26, 2023	- -

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Primary dilated cardiomyopathy;C0007194:Hypertrophic cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.85

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over