4-94634781-C-T

Position:

• chr4-94634781-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.1109-5495C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,054 control chromosomes in the GnomAD database, including 10,824 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 0.35 (10824 hom., cov: 32)
• Consequence: PDLIM5 NM_006457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDLIM5	NM_006457.5	c.1109-5495C>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.1109-5495C>T		intron_variant		1	NM_006457.5	ENSP00000321746	P3

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53676 AN: 151936 Hom.: 10822 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.353 AC: 53680 AN: 152054 Hom.: 10824 Cov.: 32 AF XY: 0.362 AC XY: 26871 AN XY: 74316

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.369

Alfa AF: 0.389 Hom.: 1620

Bravo AF: 0.334

Asia WGS AF: 0.488 AC: 1695 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.9
DANN	Benign	0.85

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: rs11732668; hg19: chr4-95555932;