chr4-94641531-C-A

Variant names:

• chr4-94641531-C-A
• rs1543013
• NM_006457.5:c.1283+1081C>A

Variant summary

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

The NM_006457.5(PDLIM5):​c.1283+1081C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,880 control chromosomes in the GnomAD database, including 11,214 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 0.37 (11214 hom., cov: 32)
• Consequence: PDLIM5 NM_006457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 4 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=-0.57).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.593 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.1283+1081C>A		intron	N/A	NP_006448.5
	PDLIM5	NM_001256426.2		c.1370+1081C>A		intron	N/A	NP_001243355.2
	PDLIM5	NM_001011513.4		c.956+1081C>A		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.1283+1081C>A		intron	N/A	ENSP00000321746.4
	PDLIM5	ENST00000615540.4	TSL:1	c.1370+1081C>A		intron	N/A	ENSP00000480359.1
	PDLIM5	ENST00000542407.5	TSL:1	c.956+1081C>A		intron	N/A	ENSP00000442187.2

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55622 AN: 151762 Hom.: 11212 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.366 AC: 55637 AN: 151880 Hom.: 11214 Cov.: 32 AF XY: 0.375 AC XY: 27792 AN XY: 74190

African (AFR) AF: 0.188 AC: 7786 AN: 41440

American (AMR) AF: 0.388 AC: 5912 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1745 AN: 3468

East Asian (EAS) AF: 0.403 AC: 2078 AN: 5156

South Asian (SAS) AF: 0.611 AC: 2947 AN: 4822

European-Finnish (FIN) AF: 0.495 AC: 5199 AN: 10496

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28564 AN: 67938

Other (OTH) AF: 0.381 AC: 801 AN: 2104

Alfa AF: 0.253 Hom.: 693

Bravo AF: 0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.6
DANN	Benign	0.85
PhyloP100		-0.040
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: rs1543013; hg19: chr4-95562682;