Genetic Variant PDLIM1:p.Val33Ile (chr10-95271784-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020992.4(PDLIM1):c.97G>A(p.Val33Ile) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000125 in 1,603,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PDLIM1
NM_020992.4 missense, splice_region

Scores

Splicing: ADA: 0.02996

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.12

Publications

0 publications found

Variant links:

Genes affected

PDLIM1 (HGNC:2067): (PDZ and LIM domain 1) This gene encodes a member of the enigma protein family. The protein contains two protein interacting domains, a PDZ domain at the amino terminal end and one to three LIM domains at the carboxyl terminal. It is a cytoplasmic protein associated with the cytoskeleton. The protein may function as an adapter to bring other LIM-interacting proteins to the cytoskeleton. Pseudogenes associated with this gene are located on chromosomes 3, 14 and 17. [provided by RefSeq, Oct 2012]

PDLIM1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23998576).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020992.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM1	NM_020992.4	MANE Select	c.97G>A	p.Val33Ile	missense splice_region	Exon 2 of 7	NP_066272.1	O00151

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDLIM1	ENST00000329399.7	TSL:1 MANE Select	c.97G>A	p.Val33Ile	missense splice_region	Exon 2 of 7	ENSP00000360305.3	O00151
PDLIM1	ENST00000956300.1		c.97G>A	p.Val33Ile	missense splice_region	Exon 2 of 7	ENSP00000626359.1
PDLIM1	ENST00000862799.1		c.97G>A	p.Val33Ile	missense splice_region	Exon 2 of 7	ENSP00000532858.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000415

AC:

AN:

240990

AF XY:

0.00000768

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000900

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1451770

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721992

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32552

American (AMR)

AF:

0.00

AC:

AN:

41988

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25978

East Asian (EAS)

AF:

0.00

AC:

AN:

39398

South Asian (SAS)

AF:

0.00

AC:

AN:

83572

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1109244

Other (OTH)

AF:

0.00

AC:

AN:

59990

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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:

0.00000658

AC:

AN:

151872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74148

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41348

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67960

Other (OTH)

AF:

0.00

AC:

AN:

2084

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.11

Eigen

Benign

-0.10

Eigen_PC

Benign

0.047

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.051

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.88

PhyloP100

6.1

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.11

REVEL

Benign

0.20

Sift

Benign

0.76

Sift4G

Benign

0.50

Polyphen

0.57

Vest4

0.36

MutPred

0.60

Gain of catalytic residue at P35 (P = 0.0281)

MVP

0.52

MPC

0.39

ClinPred

0.64

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.090

gMVP

0.31

Mutation Taster

=51/49

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.030

dbscSNV1_RF

Benign

0.31

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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