4-94637703-T-C

Variant names:

• chr4-94637703-T-C
• rs11724023
• NM_006457.5:c.1109-2573T>C

Variant summary

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

The NM_006457.5(PDLIM5):​c.1109-2573T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,064 control chromosomes in the GnomAD database, including 13,839 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 0.41 (13839 hom., cov: 32)
• Consequence: PDLIM5 NM_006457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576
• Publications: 10 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.662 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.1109-2573T>C		intron	N/A	NP_006448.5
	PDLIM5	NM_001256426.2		c.1196-2573T>C		intron	N/A	NP_001243355.2
	PDLIM5	NM_001011513.4		c.782-2573T>C		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.1109-2573T>C		intron	N/A	ENSP00000321746.4
	PDLIM5	ENST00000615540.4	TSL:1	c.1196-2573T>C		intron	N/A	ENSP00000480359.1
	PDLIM5	ENST00000542407.5	TSL:1	c.782-2573T>C		intron	N/A	ENSP00000442187.2

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62895 AN: 151946 Hom.: 13824 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.414 AC: 62930 AN: 152064 Hom.: 13839 Cov.: 32 AF XY: 0.426 AC XY: 31645 AN XY: 74328

African (AFR) AF: 0.268 AC: 11122 AN: 41472

American (AMR) AF: 0.500 AC: 7649 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1803 AN: 3470

East Asian (EAS) AF: 0.553 AC: 2857 AN: 5162

South Asian (SAS) AF: 0.681 AC: 3284 AN: 4822

European-Finnish (FIN) AF: 0.525 AC: 5539 AN: 10558

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29178 AN: 67972

Other (OTH) AF: 0.417 AC: 882 AN: 2114

Alfa AF: 0.435 Hom.: 12315

Bravo AF: 0.406

Asia WGS AF: 0.605 AC: 2099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.96
DANN	Benign	0.50
PhyloP100		-0.58
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: rs11724023; hg19: chr4-95558854;