rs12500426

Positions:

• chr4-94593458-A-C
• chr4-94593458-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.920+7014A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,820 control chromosomes in the GnomAD database, including 22,387 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 0.54 (22387 hom., cov: 30)
• Consequence: PDLIM5 NM_006457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDLIM5	NM_006457.5	c.920+7014A>C		intron_variant		ENST00000317968.9	NP_006448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDLIM5	ENST00000317968.9	c.920+7014A>C		intron_variant		1	NM_006457.5	ENSP00000321746	P3

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81562 AN: 151700 Hom.: 22363 Cov.: 30

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.538 AC: 81625 AN: 151820 Hom.: 22387 Cov.: 30 AF XY: 0.527 AC XY: 39094 AN XY: 74172

Gnomad4 AFR AF: 0.610

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.539

Alfa AF: 0.530 Hom.: 38658

Bravo AF: 0.545

Asia WGS AF: 0.362 AC: 1261 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.47

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: rs12500426; hg19: chr4-95514609;