rs4635850

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014476.6(PDLIM3):c.906C>T(p.Val302Val) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 1,613,280 control chromosomes in the GnomAD database, including 549,789 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 41055 hom., cov: 32)

Exomes 𝑓: 0.83 ( 508734 hom. )

Consequence

PDLIM3
NM_014476.6 splice_region, synonymous

Scores

Splicing: ADA: 0.0005494

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.57

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:

PDLIM3 (HGNC:):

PDLIM3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 4-185502483-G-A is Benign according to our data. Variant chr4-185502483-G-A is described in ClinVar as [Benign]. Clinvar id is 138675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-185502483-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDLIM3	NM_014476.6 linkuse as main transcript	c.906C>T	p.Val302Val	splice_region_variant, synonymous_variant	8/8	ENST00000284767.12	NP_055291.2	Q53GG5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDLIM3	ENST00000284767.12 linkuse as main transcript	c.906C>T	p.Val302Val	splice_region_variant, synonymous_variant	8/8	5	NM_014476.6	ENSP00000284767.8		Q53GG5-1

Frequencies

GnomAD3 genomes

AF:

0.705

AC:

107232

AN:

152010

Hom.:

41049

Cov.:

show subpopulations

Gnomad AFR

AF:

0.379

Gnomad AMI

AF:

0.880

Gnomad AMR

AF:

0.757

Gnomad ASJ

AF:

0.748

Gnomad EAS

AF:

0.814

Gnomad SAS

AF:

0.729

Gnomad FIN

AF:

0.868

Gnomad MID

AF:

0.680

Gnomad NFE

AF:

0.852

Gnomad OTH

AF:

0.705

GnomAD3 exomes

AF:

0.787

AC:

197765

AN:

251144

Hom.:

79766

AF XY:

0.796

AC XY:

108032

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.369

Gnomad AMR exome

AF:

0.751

Gnomad ASJ exome

AF:

0.750

Gnomad EAS exome

AF:

0.811

Gnomad SAS exome

AF:

0.747

Gnomad FIN exome

AF:

0.874

Gnomad NFE exome

AF:

0.852

Gnomad OTH exome

AF:

0.794

GnomAD4 exome

AF:

0.830

AC:

1212881

AN:

1461154

Hom.:

508734

Cov.:

AF XY:

0.829

AC XY:

602772

AN XY:

726952

show subpopulations

Gnomad4 AFR exome

AF:

0.365

Gnomad4 AMR exome

AF:

0.749

Gnomad4 ASJ exome

AF:

0.753

Gnomad4 EAS exome

AF:

0.820

Gnomad4 SAS exome

AF:

0.752

Gnomad4 FIN exome

AF:

0.877

Gnomad4 NFE exome

AF:

0.856

Gnomad4 OTH exome

AF:

0.791

GnomAD4 genome

AF:

0.705

AC:

107263

AN:

152126

Hom.:

41055

Cov.:

AF XY:

0.708

AC XY:

52662

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.379

Gnomad4 AMR

AF:

0.756

Gnomad4 ASJ

AF:

0.748

Gnomad4 EAS

AF:

0.814

Gnomad4 SAS

AF:

0.728

Gnomad4 FIN

AF:

0.868

Gnomad4 NFE

AF:

0.852

Gnomad4 OTH

AF:

0.708

Alfa

AF:

0.814

Hom.:

85485

Bravo

AF:

0.682

Asia WGS

AF:

0.734

AC:

2551

AN:

3478

EpiCase

AF:

0.842

EpiControl

AF:

0.842

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 26, 2014	This is a RefSeq error. The reference base (c.906C) is the minor allele. This al lele (C) has been identified in 15% (1260/8600) of European American chromosomes and 61% (2685/4406) of African American chromosomes by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS/; dbSNP rs1134008) and thus meets c riteria to be classified as benign. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 22, 2013	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. -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Feb 07, 2019	This alteration is classified as 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, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 04, 2023	- -

Primary dilated cardiomyopathy;C0007194:Hypertrophic cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.069

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00055

dbscSNV1_RF

Benign

0.088

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