rs6812098

Variant names:

• chr4-94561224-T-C
• rs6812098
• NM_006457.5:c.249-12127T>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.249-12127T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,062 control chromosomes in the GnomAD database, including 5,726 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 0.23 (5726 hom., cov: 32)
• Consequence: PDLIM5 NM_006457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDLIM5	NM_006457.5	c.249-12127T>C		intron_variant	Intron 3 of 12	ENST00000317968.9	NP_006448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDLIM5	ENST00000317968.9	c.249-12127T>C		intron_variant	Intron 3 of 12	1	NM_006457.5	ENSP00000321746.4

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35596 AN: 151944 Hom.: 5709 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0228

Gnomad SAS AF: 0.0621

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.234 AC: 35658 AN: 152062 Hom.: 5726 Cov.: 32 AF XY: 0.226 AC XY: 16833 AN XY: 74358

African (AFR) AF: 0.463 AC: 19183 AN: 41416

American (AMR) AF: 0.147 AC: 2249 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 438 AN: 3466

East Asian (EAS) AF: 0.0230 AC: 119 AN: 5170

South Asian (SAS) AF: 0.0623 AC: 301 AN: 4828

European-Finnish (FIN) AF: 0.111 AC: 1178 AN: 10586

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11447 AN: 67996

Other (OTH) AF: 0.209 AC: 442 AN: 2114

Alfa AF: 0.184 Hom.: 1585

Bravo AF: 0.247

Asia WGS AF: 0.0680 AC: 237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.60
PhyloP100		-0.15
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: rs6812098; hg19: chr4-95482375;