NM_006457.5:c.96+3206A>G

Variant names:

• chr4-94458590-A-G
• rs2433322
• NM_006457.5:c.96+3206A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006457.5(PDLIM5):​c.96+3206A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,840 control chromosomes in the GnomAD database, including 10,671 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 0.36 (10671 hom., cov: 31)
• Consequence: PDLIM5 NM_006457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006457.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM5	NM_006457.5	MANE Select	c.96+3206A>G		intron	N/A	NP_006448.5
	PDLIM5	NM_001256426.2		c.96+3206A>G		intron	N/A	NP_001243355.2
	PDLIM5	NM_001011513.4		c.96+3206A>G		intron	N/A	NP_001011513.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM5	ENST00000317968.9	TSL:1 MANE Select	c.96+3206A>G		intron	N/A	ENSP00000321746.4
	PDLIM5	ENST00000615540.4	TSL:1	c.96+3206A>G		intron	N/A	ENSP00000480359.1
	PDLIM5	ENST00000542407.5	TSL:1	c.96+3206A>G		intron	N/A	ENSP00000442187.2

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55195 AN: 151722 Hom.: 10668 Cov.: 31

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.364 AC: 55219 AN: 151840 Hom.: 10671 Cov.: 31 AF XY: 0.357 AC XY: 26493 AN XY: 74196

African (AFR) AF: 0.272 AC: 11269 AN: 41392

American (AMR) AF: 0.328 AC: 4998 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1415 AN: 3466

East Asian (EAS) AF: 0.184 AC: 952 AN: 5160

South Asian (SAS) AF: 0.209 AC: 1008 AN: 4820

European-Finnish (FIN) AF: 0.396 AC: 4161 AN: 10510

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29989 AN: 67938

Other (OTH) AF: 0.407 AC: 859 AN: 2108

Alfa AF: 0.408 Hom.: 31024

Bravo AF: 0.352

Asia WGS AF: 0.187 AC: 648 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.014
DANN	Benign	0.44
PhyloP100		-1.8
Mutation Taster		=100/0	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: rs2433322; hg19: chr4-95379741;