4-94628779-T-A

Position:

• chr4-94628779-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000317968.9(PDLIM5):​c.1108+10588T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0248 in 152,252 control chromosomes in the GnomAD database, including 165 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 0.025 (165 hom., cov: 32)
• Consequence: PDLIM5 ENST00000317968.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.768

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDLIM5	NM_006457.5	c.1108+10588T>A		intron_variant		ENST00000317968.9	NP_006448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDLIM5	ENST00000317968.9	c.1108+10588T>A		intron_variant		1	NM_006457.5	ENSP00000321746	P3

Frequencies

GnomAD3 genomes AF: 0.0248 AC: 3766 AN: 152134 Hom.: 164 Cov.: 32

Gnomad AFR AF: 0.00377

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.0567

Gnomad FIN AF: 0.0283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00841

Gnomad OTH AF: 0.0196

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

GnomAD4 genome AF: 0.0248 AC: 3783 AN: 152252 Hom.: 165 Cov.: 32 AF XY: 0.0290 AC XY: 2156 AN XY: 74450

Gnomad4 AFR AF: 0.00375

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.0572

Gnomad4 FIN AF: 0.0283

Gnomad4 NFE AF: 0.00840

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.0143 Hom.: 18

Bravo AF: 0.0316

Asia WGS AF: 0.102 AC: 353 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	15
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs10516953; hg19: chr4-95549930;