rs1007602

chr5-132266473-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003687.4(PDLIM4):c.255T>C(p.Gly85=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232

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]

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]

ACMG classification

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/exons	MANE	UniProt
PDLIM4	NM_003687.4	c.255T>C	p.Gly85=	synonymous_variant	3/7	ENST00000253754.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDLIM4	ENST00000253754.8	c.255T>C	p.Gly85=	synonymous_variant	3/7	1	NM_003687.4	P1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89591 AN: 151960 Hom.: 27067 Cov.: 33

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

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.: 31 AF XY: 0.604 AC XY: 437430 AN XY: 723992

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.: 33 AF XY: 0.573 AC XY: 42624 AN XY: 74324

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	12
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

Other links and lift over

dbSNP: rs1007602; hg19: chr5-131602166; COSMIC: COSV53804212; COSMIC: COSV53804212;