rs6830074

Variant names:

• chr4-94561060-G-T
• rs6830074
• NM_006457.5:c.249-12291G>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.249-12291G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 151,902 control chromosomes in the GnomAD database, including 8,208 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 0.28 (8208 hom., cov: 32)
• Consequence: PDLIM5 NM_006457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 5 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDLIM5	NM_006457.5	c.249-12291G>T		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.249-12291G>T		intron_variant	Intron 3 of 12	1	NM_006457.5	ENSP00000321746.4

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41941 AN: 151784 Hom.: 8178 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0740

Gnomad SAS AF: 0.0846

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.277 AC: 42022 AN: 151902 Hom.: 8208 Cov.: 32 AF XY: 0.269 AC XY: 19942 AN XY: 74238

African (AFR) AF: 0.562 AC: 23213 AN: 41334

American (AMR) AF: 0.199 AC: 3036 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 501 AN: 3468

East Asian (EAS) AF: 0.0741 AC: 384 AN: 5180

South Asian (SAS) AF: 0.0851 AC: 410 AN: 4816

European-Finnish (FIN) AF: 0.124 AC: 1312 AN: 10554

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.181 AC: 12311 AN: 67984

Other (OTH) AF: 0.255 AC: 535 AN: 2102

Alfa AF: 0.235 Hom.: 1051

Bravo AF: 0.295

Asia WGS AF: 0.124 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.63
PhyloP100		0.052
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: rs6830074; hg19: chr4-95482211;