rs6853490

chr4-94623567-A-Gchr4-94623567-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.1108+5376A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,976 control chromosomes in the GnomAD database, including 13,107 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 0.40 (13107 hom., cov: 32)
• Consequence: PDLIM5 NM_006457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

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=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDLIM5	NM_006457.5	c.1108+5376A>G		intron_variant		ENST00000317968.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDLIM5	ENST00000317968.9	c.1108+5376A>G		intron_variant		1	NM_006457.5	P3

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60108 AN: 151858 Hom.: 13093 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.396 AC: 60139 AN: 151976 Hom.: 13107 Cov.: 32 AF XY: 0.407 AC XY: 30251 AN XY: 74266

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.396

Alfa AF: 0.410 Hom.: 3395

Bravo AF: 0.381

Asia WGS AF: 0.578 AC: 2005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	1.1
Dann	Benign	0.83

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: rs6853490; hg19: chr4-95544718;