dbSNP rs1007602: PDLIM4:p.Gly85Gly (chr5-132266473-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003687.4(PDLIM4):c.255T>C(p.Gly85Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,606,844 control chromosomes in the GnomAD database, including 307,960 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.59 ( 27102 hom., cov: 33)

Exomes 𝑓: 0.61 ( 280858 hom. )

Consequence

PDLIM4
NM_003687.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.232

Variant links:

Genes affected

PDLIM4 (HGNC:16501): (PDZ and LIM domain 4) Enables alpha-actinin binding activity; protein homodimerization activity; and protein phosphatase binding activity. Involved in actin cytoskeleton reorganization. Located in several cellular components, including lamellipodium; perinuclear region of cytoplasm; and stress fiber. Part of filamentous actin. Implicated in osteoporosis. [provided by Alliance of Genome Resources, Apr 2022]

PDLIM4 links:

P4HA2 (HGNC:8547): (prolyl 4-hydroxylase subunit alpha 2) This gene encodes a component of prolyl 4-hydroxylase, a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one of several different types of alpha subunits and provides the major part of the catalytic site of the active enzyme. In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper three-dimensional folding of newly synthesized procollagen chains. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

P4HA2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP7

Synonymous conserved (PhyloP=-0.232 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDLIM4	NM_003687.4 link	c.255T>C	p.Gly85Gly	synonymous_variant	Exon 3 of 7	ENST00000253754.8	NP_003678.2	P50479-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDLIM4	ENST00000253754.8 link	c.255T>C	p.Gly85Gly	synonymous_variant	Exon 3 of 7	1	NM_003687.4	ENSP00000253754.3		P50479-1

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89591

AN:

151960

Hom.:

27067

Cov.:

show subpopulations

Gnomad AFR

AF:

0.599

Gnomad AMI

AF:

0.887

Gnomad AMR

AF:

0.532

Gnomad ASJ

AF:

0.646

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.474

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.645

Gnomad OTH

AF:

0.602

GnomAD3 exomes

AF:

0.536

AC:

133383

AN:

249020

Hom.:

37853

AF XY:

0.531

AC XY:

71505

AN XY:

134718

show subpopulations

Gnomad AFR exome

AF:

0.596

Gnomad AMR exome

AF:

0.432

Gnomad ASJ exome

AF:

0.651

Gnomad EAS exome

AF:

0.338

Gnomad SAS exome

AF:

0.333

Gnomad FIN exome

AF:

0.478

Gnomad NFE exome

AF:

0.644

Gnomad OTH exome

AF:

0.578

GnomAD4 exome

AF:

0.612

AC:

890575

AN:

1454766

Hom.:

280858

Cov.:

AF XY:

0.604

AC XY:

437430

AN XY:

723992

show subpopulations

Gnomad4 AFR exome

AF:

0.603

Gnomad4 AMR exome

AF:

0.445

Gnomad4 ASJ exome

AF:

0.657

Gnomad4 EAS exome

AF:

0.339

Gnomad4 SAS exome

AF:

0.338

Gnomad4 FIN exome

AF:

0.478

Gnomad4 NFE exome

AF:

0.657

Gnomad4 OTH exome

AF:

0.596

GnomAD4 genome

AF:

0.590

AC:

89670

AN:

152078

Hom.:

27102

Cov.:

AF XY:

0.573

AC XY:

42624

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.599

Gnomad4 AMR

AF:

0.532

Gnomad4 ASJ

AF:

0.646

Gnomad4 EAS

AF:

0.339

Gnomad4 SAS

AF:

0.329

Gnomad4 FIN

AF:

0.474

Gnomad4 NFE

AF:

0.645

Gnomad4 OTH

AF:

0.603

Alfa

AF:

0.633

Hom.:

53254

Bravo

AF:

0.597

Asia WGS

AF:

0.359

AC:

1253

AN:

3478

EpiCase

AF:

0.654

EpiControl

AF:

0.656

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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