Genetic Variant PADI4:p.Gly55Ser (chr1-17331039-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_012387.3(PADI4):c.163G>A(p.Gly55Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 1,607,640 control chromosomes in the GnomAD database, including 266,699 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,association (no stars).

Frequency

Genomes: 𝑓 0.55 ( 23311 hom., cov: 32)

Exomes 𝑓: 0.58 ( 243388 hom. )

Consequence

PADI4
NM_012387.3 missense

Scores

Clinical Significance

Benign; association no assertion criteria provided B:1O:1

Conservation

PhyloP100: -1.24

Publications

88 publications found

Variant links:

Genes affected

PADI4 (HGNC:18368): (peptidyl arginine deiminase 4) This gene is a member of a gene family which encodes enzymes responsible for the conversion of arginine residues to citrulline residues. This gene may play a role in granulocyte and macrophage development leading to inflammation and immune response. [provided by RefSeq, Jul 2008]

PADI4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2175569E-5).

BP6

Variant 1-17331039-G-A is Benign according to our data. Variant chr1-17331039-G-A is described in ClinVar as [Benign, association]. Clinvar id is 972892.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3 link	c.163G>A	p.Gly55Ser	missense_variant	Exon 2 of 16	ENST00000375448.4	NP_036519.2	Q9UM07

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4 link	c.163G>A	p.Gly55Ser	missense_variant	Exon 2 of 16	1	NM_012387.3	ENSP00000364597.4		Q9UM07
PADI4	ENST00000375453.5 link	c.163G>A	p.Gly55Ser	missense_variant	Exon 2 of 4	2		ENSP00000364602.1		B1AQ67

Frequencies

GnomAD3 genomes

AF:

0.551

AC:

83654

AN:

151870

Hom.:

23320

Cov.:

show subpopulations

Gnomad AFR

AF:

0.476

Gnomad AMI

AF:

0.649

Gnomad AMR

AF:

0.548

Gnomad ASJ

AF:

0.618

Gnomad EAS

AF:

0.593

Gnomad SAS

AF:

0.532

Gnomad FIN

AF:

0.593

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.584

Gnomad OTH

AF:

0.531

GnomAD2 exomes

AF:

0.559

AC:

137546

AN:

246090

AF XY:

0.563

show subpopulations

Gnomad AFR exome

AF:

0.471

Gnomad AMR exome

AF:

0.500

Gnomad ASJ exome

AF:

0.595

Gnomad EAS exome

AF:

0.577

Gnomad FIN exome

AF:

0.590

Gnomad NFE exome

AF:

0.586

Gnomad OTH exome

AF:

0.571

GnomAD4 exome

AF:

0.577

AC:

839624

AN:

1455652

Hom.:

243388

Cov.:

AF XY:

0.576

AC XY:

417280

AN XY:

724128

show subpopulations

African (AFR)

AF:

0.471

AC:

15640

AN:

33176

American (AMR)

AF:

0.513

AC:

22513

AN:

43924

Ashkenazi Jewish (ASJ)

AF:

0.604

AC:

15697

AN:

25994

East Asian (EAS)

AF:

0.592

AC:

23206

AN:

39184

South Asian (SAS)

AF:

0.528

AC:

45063

AN:

85338

European-Finnish (FIN)

AF:

0.587

AC:

31352

AN:

53378

Middle Eastern (MID)

AF:

0.559

AC:

3216

AN:

5750

European-Non Finnish (NFE)

AF:

0.586

AC:

649292

AN:

1108730

Other (OTH)

AF:

0.559

AC:

33645

AN:

60178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

17005

34010

51014

68019

85024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.551

AC:

83679

AN:

151988

Hom.:

23311

Cov.:

AF XY:

0.551

AC XY:

40952

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.476

AC:

19734

AN:

41424

American (AMR)

AF:

0.548

AC:

8366

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.618

AC:

2142

AN:

3468

East Asian (EAS)

AF:

0.593

AC:

3051

AN:

5146

South Asian (SAS)

AF:

0.531

AC:

2557

AN:

4818

European-Finnish (FIN)

AF:

0.593

AC:

6258

AN:

10554

Middle Eastern (MID)

AF:

0.585

AC:

172

AN:

294

European-Non Finnish (NFE)

AF:

0.584

AC:

39704

AN:

67992

Other (OTH)

AF:

0.524

AC:

1107

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1923

3846

5770

7693

9616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.574

Hom.:

111920

Bravo

AF:

0.543

TwinsUK

AF:

0.586

AC:

2174

ALSPAC

AF:

0.591

AC:

2279

ESP6500AA

AF:

0.485

AC:

2135

ESP6500EA

AF:

0.577

AC:

4958

ExAC

AF:

0.561

AC:

68108

Asia WGS

AF:

0.484

AC:

1682

AN:

3478

ClinVar

Significance: Benign; association

Submissions summary: Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PADI4-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Rheumatoid arthritis;C5441745:Abnormal pulmonary interstitial morphology

Other:1

Feb 01, 2020

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance:association

Review Status:no assertion criteria provided

Collection Method:case-control

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.91

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0020

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.0036

T;T

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0051

MetaRNN

Benign

0.000012

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.1

.;N

PhyloP100

-1.2

PrimateAI

Benign

0.20

PROVEAN

Benign

1.5

N;N

REVEL

Benign

0.025

Sift

Benign

1.0

T;T

Sift4G

Benign

0.80

T;T

Polyphen

0.0

.;B

Vest4

0.022

MPC

0.11

ClinPred

0.042

GERP RS

-11

Varity_R

0.038

gMVP

0.13

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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chr1-17331039-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over