rs1007602

Variant names:

• chr5-132266473-T-C
• rs1007602
• NM_003687.4:c.255T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232
• Publications: 43 publications found

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]

P4HA2 Gene-Disease associations (from GenCC):

• myopia

  Inheritance: AD Classification: STRONG Submitted by: G2P
• myopia 25, autosomal dominant

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003687.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM4	NM_003687.4	MANE Select	c.255T>C	p.Gly85Gly	synonymous	Exon 3 of 7	NP_003678.2
	PDLIM4	NM_001131027.2		c.255T>C	p.Gly85Gly	synonymous	Exon 3 of 6	NP_001124499.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM4	ENST00000253754.8	TSL:1 MANE Select	c.255T>C	p.Gly85Gly	synonymous	Exon 3 of 7	ENSP00000253754.3
	PDLIM4	ENST00000379018.7	TSL:1	c.255T>C	p.Gly85Gly	synonymous	Exon 3 of 6	ENSP00000368303.3
	P4HA2	ENST00000471826.1	TSL:1	n.458+10869A>G		intron	N/A

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

GnomAD2 exomes AF: 0.536 AC: 133383 AN: 249020 AF XY: 0.531

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 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

African (AFR) AF: 0.603 AC: 20135 AN: 33372

American (AMR) AF: 0.445 AC: 19817 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 17144 AN: 26078

East Asian (EAS) AF: 0.339 AC: 13438 AN: 39606

South Asian (SAS) AF: 0.338 AC: 29078 AN: 85968

European-Finnish (FIN) AF: 0.478 AC: 25453 AN: 53254

Middle Eastern (MID) AF: 0.532 AC: 3055 AN: 5740

European-Non Finnish (NFE) AF: 0.657 AC: 726603 AN: 1106016

Other (OTH) AF: 0.596 AC: 35852 AN: 60166

GnomAD4 genome AF: 0.590 AC: 89670 AN: 152078 Hom.: 27102 Cov.: 33 AF XY: 0.573 AC XY: 42624 AN XY: 74324

African (AFR) AF: 0.599 AC: 24861 AN: 41478

American (AMR) AF: 0.532 AC: 8123 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2241 AN: 3468

East Asian (EAS) AF: 0.339 AC: 1750 AN: 5160

South Asian (SAS) AF: 0.329 AC: 1582 AN: 4814

European-Finnish (FIN) AF: 0.474 AC: 5019 AN: 10582

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.645 AC: 43844 AN: 67978

Other (OTH) AF: 0.603 AC: 1277 AN: 2116

Alfa AF: 0.634 Hom.: 66566

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		-0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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