rs11097431

chr4-94585691-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_006457.5(PDLIM5):c.837G>A(p.Gln279=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,612,494 control chromosomes in the GnomAD database, including 34,913 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 0.21 (3648 hom., cov: 31)
  • Exomes 𝑓: 0.20 (31265 hom.)
• Consequence: PDLIM5 NM_006457.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.24

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=3.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDLIM5	NM_006457.5	c.837G>A	p.Gln279=	synonymous_variant	6/13	ENST00000317968.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDLIM5	ENST00000317968.9	c.837G>A	p.Gln279=	synonymous_variant	6/13	1	NM_006457.5	P3

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32292 AN: 151890 Hom.: 3650 Cov.: 31

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0999

Gnomad SAS AF: 0.0948

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.216

GnomAD3 exomes AF: 0.177 AC: 44466 AN: 251220 Hom.: 4392 AF XY: 0.173 AC XY: 23482 AN XY: 135782

Gnomad AFR exome AF: 0.266

Gnomad AMR exome AF: 0.155

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.0922

Gnomad SAS exome AF: 0.0929

Gnomad FIN exome AF: 0.148

Gnomad NFE exome AF: 0.215

Gnomad OTH exome AF: 0.188

GnomAD4 exome AF: 0.201 AC: 293845 AN: 1460486 Hom.: 31265 Cov.: 32 AF XY: 0.197 AC XY: 142864 AN XY: 726592

Gnomad4 AFR exome AF: 0.270

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.0956

Gnomad4 SAS exome AF: 0.0926

Gnomad4 FIN exome AF: 0.154

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.213 AC: 32319 AN: 152008 Hom.: 3648 Cov.: 31 AF XY: 0.205 AC XY: 15199 AN XY: 74278

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.100

Gnomad4 SAS AF: 0.0953

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.214

Alfa AF: 0.215 Hom.: 2183

Bravo AF: 0.217

Asia WGS AF: 0.126 AC: 439 AN: 3478

EpiCase AF: 0.211

EpiControl AF: 0.205

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	7.8
Dann	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs11097431; hg19: chr4-95506842; COSMIC: COSV58747368; COSMIC: COSV58747368;