rs3762876

Variant names:

• chr4-94668326-A-G
• rs3762876
• NM_006457.5:c.*4259A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-94668326-A-G
• chr4-94668326-A-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.*4259A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,016 control chromosomes in the GnomAD database, including 7,782 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 0.32 (7782 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PDLIM5 NM_006457.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• 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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDLIM5	NM_006457.5	c.*4259A>G		downstream_gene_variant		ENST00000317968.9	NP_006448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDLIM5	ENST00000317968.9	c.*4259A>G		downstream_gene_variant		1	NM_006457.5	ENSP00000321746.4
PDLIM5	ENST00000615540.4	c.*4259A>G		downstream_gene_variant		1		ENSP00000480359.1
PDLIM5	ENST00000437932.5	c.*4259A>G		downstream_gene_variant		5		ENSP00000398469.2

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47991 AN: 151898 Hom.: 7770 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.316 AC: 48016 AN: 152016 Hom.: 7782 Cov.: 32 AF XY: 0.315 AC XY: 23398 AN XY: 74296

African (AFR) AF: 0.258 AC: 10731 AN: 41516

American (AMR) AF: 0.298 AC: 4548 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1099 AN: 3470

East Asian (EAS) AF: 0.335 AC: 1729 AN: 5164

South Asian (SAS) AF: 0.222 AC: 1070 AN: 4818

European-Finnish (FIN) AF: 0.336 AC: 3541 AN: 10552

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24273 AN: 67922

Other (OTH) AF: 0.333 AC: 703 AN: 2110

Alfa AF: 0.342 Hom.: 7722

Bravo AF: 0.311

Asia WGS AF: 0.234 AC: 813 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.21
DANN	Benign	0.79
PhyloP100		-1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3762876; hg19: chr4-95589477;