rs1543013

Positions:

• chr4-94641531-C-A
• chr4-94641531-C-T

Variant summary

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

The ENST00000317968.9(PDLIM5):​c.1283+1081C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,880 control chromosomes in the GnomAD database, including 11,214 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 0.37 (11214 hom., cov: 32)
• Consequence: PDLIM5 ENST00000317968.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

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=-0.57).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDLIM5	NM_006457.5	c.1283+1081C>A		intron_variant		ENST00000317968.9	NP_006448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDLIM5	ENST00000317968.9	c.1283+1081C>A		intron_variant		1	NM_006457.5	ENSP00000321746	P3

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55622 AN: 151762 Hom.: 11212 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.366 AC: 55637 AN: 151880 Hom.: 11214 Cov.: 32 AF XY: 0.375 AC XY: 27792 AN XY: 74190

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.381

Alfa AF: 0.257 Hom.: 682

Bravo AF: 0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.6
DANN	Benign	0.85

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: rs1543013; hg19: chr4-95562682;