dbSNP rs17021918: PDLIM5:c.1283+1276C>T (chr4-94641726-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_006457.5(PDLIM5):c.1283+1276C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.299 (AC=45,484) in the gnomAD database across 151,968 control chromosomes, including 7,112 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.347. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7112 hom., cov: 33)

Consequence

PDLIM5
NM_006457.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

Publications

118 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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new If you want to explore the variant's impact on the transcript NM_006457.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.3467 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_006457.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDLIM5	NM_006457.5	MANE Select	c.1283+1276C>T	intron	N/A	NP_006448.5	Q96HC4-1
PDLIM5	NM_001256426.2		c.1370+1276C>T	intron	N/A	NP_001243355.2	Q96HC4-6
PDLIM5	NM_001011513.4		c.956+1276C>T	intron	N/A	NP_001011513.4	Q96HC4-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDLIM5	ENST00000317968.9	TSL:1 MANE Select	c.1283+1276C>T	intron	N/A	ENSP00000321746.4	Q96HC4-1
PDLIM5	ENST00000615540.4	TSL:1	c.1370+1276C>T	intron	N/A	ENSP00000480359.1	Q96HC4-6
PDLIM5	ENST00000542407.5	TSL:1	c.956+1276C>T	intron	N/A	ENSP00000442187.2	Q96HC4-4

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45454

AN:

151848

Hom.:

7101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.349

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.350

Gnomad OTH

AF:

0.321

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

GnomAD4 genome

AF:

0.299

AC:

45484

AN:

151968

Hom.:

7112

Cov.:

AF XY:

0.298

AC XY:

22120

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.219

AC:

9090

AN:

41478

American (AMR)

AF:

0.283

AC:

4316

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1095

AN:

3468

East Asian (EAS)

AF:

0.349

AC:

1795

AN:

5146

South Asian (SAS)

AF:

0.191

AC:

920

AN:

4824

European-Finnish (FIN)

AF:

0.331

AC:

3491

AN:

10548

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.350

AC:

23805

AN:

67930

Other (OTH)

AF:

0.317

AC:

669

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1637

3274

4912

6549

8186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.336

Hom.:

31941

Bravo

AF:

0.293

Asia WGS

AF:

0.229

AC:

795

AN:

3472

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.373

AC:

45676

AN:

122552

Turkish Variome

AF:

0.329

AC:

508

AN:

1546

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.343

AC:

3069

AN:

8960

Hom.:

542

ABraOM SABE-WGS-1171

AF:

0.311

AC:

728

AN:

2342

Hom.:

111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.9

(source)

DANN

Benign

0.58

PhyloP100

-1.0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over