rs2438146

Positions:

• chr4-94474237-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.96+18853C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,978 control chromosomes in the GnomAD database, including 11,187 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 (11187 hom., cov: 32)
• Consequence: PDLIM5 NM_006457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313

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]

PDLIM5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDLIM5	NM_006457.5	c.96+18853C>T		intron_variant		ENST00000317968.9	NP_006448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDLIM5	ENST00000317968.9	c.96+18853C>T		intron_variant		1	NM_006457.5	ENSP00000321746.4

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56511 AN: 151860 Hom.: 11184 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.372 AC: 56530 AN: 151978 Hom.: 11187 Cov.: 32 AF XY: 0.365 AC XY: 27125 AN XY: 74312

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.419

Alfa AF: 0.422 Hom.: 6671

Bravo AF: 0.361

Asia WGS AF: 0.189 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.94
DANN	Benign	0.70

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: rs2438146; hg19: chr4-95395388; COSMIC: COSV58752018;