Genetic Variant PDLIM3:p.Val358Ile (chr4-185502317-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014476.6(PDLIM3):c.1072G>A(p.Val358Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V358V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

PDLIM3
NM_014476.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.14

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
dilated cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

PDLIM3 links:

ENSG00000249679 (HGNC:58917):

ENSG00000249679 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25372374).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014476.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDLIM3	NM_014476.6	MANE Select	c.1072G>A	p.Val358Ile	missense	Exon 8 of 8	NP_055291.2	Q53GG5-1
PDLIM3	NM_001114107.5		c.928G>A	p.Val310Ile	missense	Exon 7 of 7	NP_001107579.1	Q53GG5-2
PDLIM3	NM_001257962.2		c.808G>A	p.Val270Ile	missense	Exon 7 of 7	NP_001244891.1	A0A087WYF8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDLIM3	ENST00000284767.12	TSL:5 MANE Select	c.1072G>A	p.Val358Ile	missense	Exon 8 of 8	ENSP00000284767.8	Q53GG5-1
PDLIM3	ENST00000284771.7	TSL:1	c.928G>A	p.Val310Ile	missense	Exon 7 of 7	ENSP00000284771.6	Q53GG5-2
PDLIM3	ENST00000284770.10	TSL:1	c.571G>A	p.Val191Ile	missense	Exon 5 of 5	ENSP00000284770.5	A0A2U3TZH4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary dilated cardiomyopathy;C0007194:Hypertrophic cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Benign

-0.021

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.015

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

PhyloP100

4.1

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.68

REVEL

Benign

0.078

Sift

Uncertain

0.027

Sift4G

Uncertain

0.034

Polyphen

0.0010

Vest4

0.25

MutPred

0.20

Gain of glycosylation at T357 (P = 0.0115)

MVP

0.39

MPC

0.13

ClinPred

0.84

GERP RS

4.5

Varity_R

0.090

gMVP

0.18

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over