Genetic Variant NM_020992.4:c.524A>G (chr10-95263873-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_020992.4(PDLIM1):c.524A>G(p.Asn175Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,610,756 control chromosomes in the GnomAD database, including 67,499 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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 ( 5253 hom., cov: 31)

Exomes 𝑓: 0.29 ( 62246 hom. )

Consequence

PDLIM1
NM_020992.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.856

Publications

29 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0047923923).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDLIM1	NM_020992.4 link	c.524A>G	p.Asn175Ser	missense_variant	Exon 4 of 7	ENST00000329399.7	NP_066272.1	O00151V9HW92

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PDLIM1	ENST00000329399.7 link	c.524A>G	p.Asn175Ser	missense_variant	Exon 4 of 7	1	NM_020992.4	ENSP00000360305.3	O00151
PDLIM1	ENST00000477757.5 link	n.469A>G		non_coding_transcript_exon_variant	Exon 3 of 6	2
PDLIM1	ENST00000493949.1 link	n.*3A>G		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.255

AC:

38752

AN:

151914

Hom.:

5255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.408

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.0259

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.307

Gnomad OTH

AF:

0.261

GnomAD2 exomes

AF:

0.254

AC:

63090

AN:

248446

AF XY:

0.255

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.270

Gnomad ASJ exome

AF:

0.248

Gnomad EAS exome

AF:

0.0188

Gnomad FIN exome

AF:

0.269

Gnomad NFE exome

AF:

0.301

Gnomad OTH exome

AF:

0.278

GnomAD4 exome

AF:

0.287

AC:

418580

AN:

1458724

Hom.:

62246

Cov.:

AF XY:

0.286

AC XY:

207374

AN XY:

725522

show subpopulations

African (AFR)

AF:

0.183

AC:

6114

AN:

33458

American (AMR)

AF:

0.270

AC:

12054

AN:

44628

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

6546

AN:

25942

East Asian (EAS)

AF:

0.0362

AC:

1435

AN:

39694

South Asian (SAS)

AF:

0.229

AC:

19678

AN:

85892

European-Finnish (FIN)

AF:

0.272

AC:

14482

AN:

53332

Middle Eastern (MID)

AF:

0.226

AC:

1224

AN:

5412

European-Non Finnish (NFE)

AF:

0.307

AC:

340829

AN:

1110114

Other (OTH)

AF:

0.269

AC:

16218

AN:

60252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

14283

28566

42849

57132

71415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11006

22012

33018

44024

55030

<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:

0.255

AC:

38766

AN:

152032

Hom.:

5253

Cov.:

AF XY:

0.251

AC XY:

18647

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.193

AC:

8007

AN:

41466

American (AMR)

AF:

0.270

AC:

4118

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

859

AN:

3466

East Asian (EAS)

AF:

0.0261

AC:

135

AN:

5164

South Asian (SAS)

AF:

0.221

AC:

1067

AN:

4820

European-Finnish (FIN)

AF:

0.258

AC:

2727

AN:

10574

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.307

AC:

20873

AN:

67956

Other (OTH)

AF:

0.257

AC:

543

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1424

2848

4273

5697

7121

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:

0.277

Hom.:

4058

Bravo

AF:

0.253

TwinsUK

AF:

0.312

AC:

1156

ALSPAC

AF:

0.299

AC:

1154

ESP6500AA

AF:

0.195

AC:

861

ESP6500EA

AF:

0.294

AC:

2530

ExAC

AF:

0.251

AC:

30496

Asia WGS

AF:

0.139

AC:

481

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.2

(source)

DANN

Benign

0.20

DEOGEN2

Benign

0.085

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0048

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.20

PhyloP100

0.86

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.37

REVEL

Benign

0.031

Sift

Benign

1.0

Sift4G

Benign

0.87

Polyphen

0.0010

Vest4

0.068

MPC

0.15

ClinPred

0.0042

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.051

gMVP

0.13

Mutation Taster

=98/2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over