NM_006457.5:c.1283+1276C>T

Variant names:

• chr4-94641726-C-T
• rs17021918
• NM_006457.5:c.1283+1276C>T

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+1276C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,968 control chromosomes in the GnomAD database, including 7,112 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 0.30 (7112 hom., cov: 33)
• Consequence: PDLIM5 NM_006457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 118 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.347 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM5	NM_006457.5	MANE Select	c.1283+1276C>T		intron	N/A	NP_006448.5	Q96HC4-1
	PDLIM5	NM_001256426.2		c.1370+1276C>T		intron	N/A	NP_001243355.2	Q96HC4-6
	PDLIM5	NM_001011513.4		c.956+1276C>T		intron	N/A	NP_001011513.4	Q96HC4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM5	ENST00000317968.9	TSL:1 MANE Select	c.1283+1276C>T		intron	N/A	ENSP00000321746.4	Q96HC4-1
	PDLIM5	ENST00000615540.4	TSL:1	c.1370+1276C>T		intron	N/A	ENSP00000480359.1	Q96HC4-6
	PDLIM5	ENST00000542407.5	TSL:1	c.956+1276C>T		intron	N/A	ENSP00000442187.2	Q96HC4-4

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45454 AN: 151848 Hom.: 7101 Cov.: 33

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.299 AC: 45484 AN: 151968 Hom.: 7112 Cov.: 33 AF XY: 0.298 AC XY: 22120 AN XY: 74280

African (AFR) AF: 0.219 AC: 9090 AN: 41478

American (AMR) AF: 0.283 AC: 4316 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1095 AN: 3468

East Asian (EAS) AF: 0.349 AC: 1795 AN: 5146

South Asian (SAS) AF: 0.191 AC: 920 AN: 4824

European-Finnish (FIN) AF: 0.331 AC: 3491 AN: 10548

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23805 AN: 67930

Other (OTH) AF: 0.317 AC: 669 AN: 2108

Alfa AF: 0.336 Hom.: 31941

Bravo AF: 0.293

Asia WGS AF: 0.229 AC: 795 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.58
PhyloP100		-1.0
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: rs17021918; hg19: chr4-95562877;