rs17021918

chr4-94641726-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006457.5(PDLIM5):c.1283+1276C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,968 control chromosomes in the GnomAD database, including 7,112 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 0.30 (7112 hom., cov: 33)
• Consequence: PDLIM5 NM_006457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDLIM5	NM_006457.5	c.1283+1276C>T		intron_variant		ENST00000317968.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDLIM5	ENST00000317968.9	c.1283+1276C>T		intron_variant		1	NM_006457.5	P3

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45454 AN: 151848 Hom.: 7101 Cov.: 33

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.321

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.299 AC: 45484 AN: 151968 Hom.: 7112 Cov.: 33 AF XY: 0.298 AC XY: 22120 AN XY: 74280

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.317

Alfa AF: 0.340 Hom.: 14221

Bravo AF: 0.293

Asia WGS AF: 0.229 AC: 795 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.9
Dann	Benign	0.58

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: rs17021918; hg19: chr4-95562877;