rs11097431

Variant names:

• chr4-94585691-G-A
• rs11097431
• NM_006457.5:c.837G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_006457.5(PDLIM5):​c.837G>A​(p.Gln279Gln) 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
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.08).
• 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 rank	MANE	Protein	UniProt
PDLIM5	NM_006457.5	c.837G>A	p.Gln279Gln	synonymous_variant	Exon 6 of 13	ENST00000317968.9	NP_006448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDLIM5	ENST00000317968.9	c.837G>A	p.Gln279Gln	synonymous_variant	Exon 6 of 13	1	NM_006457.5	ENSP00000321746.4

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

GnomAD2 exomes AF: 0.177 AC: 44466 AN: 251220 AF XY: 0.173

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 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

African (AFR) AF: 0.270 AC: 9026 AN: 33452

American (AMR) AF: 0.161 AC: 7206 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 3664 AN: 26124

East Asian (EAS) AF: 0.0956 AC: 3795 AN: 39692

South Asian (SAS) AF: 0.0926 AC: 7987 AN: 86236

European-Finnish (FIN) AF: 0.154 AC: 8204 AN: 53412

Middle Eastern (MID) AF: 0.188 AC: 1080 AN: 5758

European-Non Finnish (NFE) AF: 0.217 AC: 240793 AN: 1110750

Other (OTH) AF: 0.200 AC: 12090 AN: 60348

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

African (AFR) AF: 0.266 AC: 11037 AN: 41456

American (AMR) AF: 0.201 AC: 3068 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 494 AN: 3466

East Asian (EAS) AF: 0.100 AC: 516 AN: 5152

South Asian (SAS) AF: 0.0953 AC: 458 AN: 4806

European-Finnish (FIN) AF: 0.143 AC: 1511 AN: 10568

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14450 AN: 67966

Other (OTH) AF: 0.214 AC: 452 AN: 2112

Alfa AF: 0.211 Hom.: 3257

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
PhyloP100		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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