Genetic Variant PDLIM5:c.711-1124A>T (chr4-94584441-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006457.5(PDLIM5):c.711-1124A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,124 control chromosomes in the GnomAD database, including 5,395 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 0.25 ( 5395 hom., cov: 32)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

PDLIM5
NM_006457.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.201

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDLIM5	NM_006457.5 link	c.711-1124A>T		intron_variant	Intron 5 of 12	ENST00000317968.9	NP_006448.5	Q96HC4-1A0A024RDE8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDLIM5	ENST00000317968.9 link	c.711-1124A>T		intron_variant	Intron 5 of 12	1	NM_006457.5	ENSP00000321746.4		Q96HC4-1

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38333

AN:

151974

Hom.:

5393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.379

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.316

Gnomad OTH

AF:

0.277

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.417

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.200

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.252

AC:

38335

AN:

152092

Hom.:

5395

Cov.:

AF XY:

0.251

AC XY:

18688

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.266

Gnomad4 ASJ

AF:

0.292

Gnomad4 EAS

AF:

0.380

Gnomad4 SAS

AF:

0.135

Gnomad4 FIN

AF:

0.280

Gnomad4 NFE

AF:

0.316

Gnomad4 OTH

AF:

0.274

Alfa

AF:

0.157

Hom.:

352

Bravo

AF:

0.246

Asia WGS

AF:

0.213

AC:

743

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.70

DANN

Benign

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over