Genetic Variant PDLIM5:c.711-1124A>T (chr4-94584441-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001256426.2(PDLIM5):c.384-545A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,124 control chromosomes in the GnomAD database, including 5,395 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 0.25 ( 5395 hom., cov: 32)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

PDLIM5
NM_001256426.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.201

Publications

6 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256426.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PDLIM5	NM_006457.5	MANE Select	c.711-1124A>T	intron	N/A	NP_006448.5
PDLIM5	NM_001256426.2		c.384-545A>T	intron	N/A	NP_001243355.2
PDLIM5	NM_001011513.4		c.384-1124A>T	intron	N/A	NP_001011513.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PDLIM5	ENST00000317968.9	TSL:1 MANE Select	c.711-1124A>T	intron	N/A	ENSP00000321746.4
PDLIM5	ENST00000615540.4	TSL:1	c.384-545A>T	intron	N/A	ENSP00000480359.1
PDLIM5	ENST00000542407.5	TSL:1	c.384-1124A>T	intron	N/A	ENSP00000442187.2

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38333

AN:

151974

Hom.:

5393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.379

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.316

Gnomad OTH

AF:

0.277

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.417

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.200

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.252

AC:

38335

AN:

152092

Hom.:

5395

Cov.:

AF XY:

0.251

AC XY:

18688

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.129

AC:

5347

AN:

41508

American (AMR)

AF:

0.266

AC:

4063

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

1012

AN:

3470

East Asian (EAS)

AF:

0.380

AC:

1965

AN:

5170

South Asian (SAS)

AF:

0.135

AC:

651

AN:

4824

European-Finnish (FIN)

AF:

0.280

AC:

2958

AN:

10564

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.316

AC:

21480

AN:

67956

Other (OTH)

AF:

0.274

AC:

580

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1425

2850

4276

5701

7126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.157

Hom.:

352

Bravo

AF:

0.246

Asia WGS

AF:

0.213

AC:

743

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.70

(source)

DANN

Benign

0.78

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over