4-94584441-A-T

Variant summary

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

The NM_006457.5(PDLIM5):c.711-1124A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,124 control chromosomes in the GnomAD database, including 5,395 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 0.25 (5395 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: PDLIM5 NM_006457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201

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 (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDLIM5	NM_006457.5	c.711-1124A>T		intron_variant		ENST00000317968.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDLIM5	ENST00000317968.9	c.711-1124A>T		intron_variant		1	NM_006457.5	P3

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38333 AN: 151974 Hom.: 5393 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.250 AC: 8 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.417 AC XY: 5 AN XY: 12

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.252 AC: 38335 AN: 152092 Hom.: 5395 Cov.: 32 AF XY: 0.251 AC XY: 18688 AN XY: 74352

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.274

Alfa AF: 0.157 Hom.: 352

Bravo AF: 0.246

Asia WGS AF: 0.213 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.70
Dann	Benign	0.78

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: rs7682375; hg19: chr4-95505592;