Variant 4-94575789-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The ENST00000317968.9(PDLIM5):c.465G>A(p.Ala155=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,613,928 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 13 hom., cov: 32)

Exomes 𝑓: 0.015 ( 249 hom. )

Consequence

PDLIM5
ENST00000317968.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.910

Variant links:

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]

PDLIM5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 4-94575789-G-A is Benign according to our data. Variant chr4-94575789-G-A is described in ClinVar as [Benign]. Clinvar id is 777394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.91 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00894 (1359/152078) while in subpopulation NFE AF= 0.0161 (1092/67986). AF 95% confidence interval is 0.0153. There are 13 homozygotes in gnomad4. There are 590 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1359 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDLIM5	NM_006457.5 linkuse as main transcript	c.465G>A	p.Ala155=	synonymous_variant	5/13	ENST00000317968.9	NP_006448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDLIM5	ENST00000317968.9 linkuse as main transcript	c.465G>A	p.Ala155=	synonymous_variant	5/13	1	NM_006457.5	ENSP00000321746	P3	Q96HC4-1

Frequencies

GnomAD3 genomes

AF:

0.00894

AC:

1358

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00305

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00485

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0160

Gnomad OTH

AF:

0.00913

GnomAD3 exomes

AF:

0.00880

AC:

2211

AN:

251296

Hom.:

AF XY:

0.00895

AC XY:

1215

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.00326

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.00337

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00343

Gnomad FIN exome

AF:

0.00375

Gnomad NFE exome

AF:

0.0156

Gnomad OTH exome

AF:

0.00766

GnomAD4 exome

AF:

0.0155

AC:

22625

AN:

1461850

Hom.:

249

Cov.:

AF XY:

0.0151

AC XY:

10980

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00278

Gnomad4 AMR exome

AF:

0.00335

Gnomad4 ASJ exome

AF:

0.00298

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00388

Gnomad4 FIN exome

AF:

0.00348

Gnomad4 NFE exome

AF:

0.0188

Gnomad4 OTH exome

AF:

0.0134

GnomAD4 genome

AF:

0.00894

AC:

1359

AN:

152078

Hom.:

Cov.:

AF XY:

0.00794

AC XY:

590

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00301

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00415

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.0161

Gnomad4 OTH

AF:

0.00903

Alfa

AF:

0.0128

Hom.:

Bravo

AF:

0.00962

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0167

EpiControl

AF:

0.0158

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.70

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over