Genetic Variant PDLIM5:p.Pro90Ala (chr4-94573370-C-G) – 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_006457.5(PDLIM5):c.268C>G(p.Pro90Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P90S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PDLIM5
NM_006457.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.978

Publications

0 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]

PDLIM5 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=0.12588745).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006457.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDLIM5	NM_006457.5	MANE Select	c.268C>G	p.Pro90Ala	missense	Exon 4 of 13	NP_006448.5	Q96HC4-1
PDLIM5	NM_001256426.2		c.268C>G	p.Pro90Ala	missense	Exon 4 of 17	NP_001243355.2	Q96HC4-6
PDLIM5	NM_001011513.4		c.268C>G	p.Pro90Ala	missense	Exon 4 of 13	NP_001011513.4	Q96HC4-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDLIM5	ENST00000317968.9	TSL:1 MANE Select	c.268C>G	p.Pro90Ala	missense	Exon 4 of 13	ENSP00000321746.4	Q96HC4-1
PDLIM5	ENST00000615540.4	TSL:1	c.268C>G	p.Pro90Ala	missense	Exon 4 of 17	ENSP00000480359.1	Q96HC4-6
PDLIM5	ENST00000542407.5	TSL:1	c.268C>G	p.Pro90Ala	missense	Exon 4 of 13	ENSP00000442187.2	Q96HC4-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251326

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.29

Eigen

Benign

-0.052

Eigen_PC

Benign

-0.0018

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.012

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

0.98

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.5

REVEL

Benign

0.016

Sift

Benign

0.15

Sift4G

Benign

0.23

Polyphen

0.0

Vest4

0.26

MutPred

0.17

Loss of glycosylation at P90 (P = 0.0449)

MVP

0.61

MPC

0.11

ClinPred

0.098

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.051

gMVP

0.25

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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