chr4-94589945-T-C

Position:

• chr4-94589945-T-C

Variant summary

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

The NM_006457.5(PDLIM5):​c.920+3501T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,762 control chromosomes in the GnomAD database, including 20,730 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 0.52 (20730 hom., cov: 30)
• Consequence: PDLIM5 NM_006457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDLIM5	NM_006457.5	c.920+3501T>C		intron_variant		ENST00000317968.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDLIM5	ENST00000317968.9	c.920+3501T>C		intron_variant		1	NM_006457.5	P3

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78543 AN: 151642 Hom.: 20708 Cov.: 30

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.518 AC: 78605 AN: 151762 Hom.: 20730 Cov.: 30 AF XY: 0.508 AC XY: 37659 AN XY: 74150

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.523

Alfa AF: 0.518 Hom.: 2561

Bravo AF: 0.524

Asia WGS AF: 0.357 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.6
DANN	Benign	0.77

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: rs10019505; hg19: chr4-95511096;