dbSNP rs34309058: PADI4:p.Pro102Thr (chr1-17333973-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_012387.3(PADI4):c.304C>A(p.Pro102Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,612,530 control chromosomes in the GnomAD database, including 241 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 0.011 ( 16 hom., cov: 30)

Exomes 𝑓: 0.015 ( 225 hom. )

Consequence

PADI4
NM_012387.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.42

Publications

8 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029465556).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0109 (1666/152240) while in subpopulation NFE AF = 0.0173 (1178/68010). AF 95% confidence interval is 0.0165. There are 16 homozygotes in GnomAd4. There are 780 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3 link	c.304C>A	p.Pro102Thr	missense_variant	Exon 3 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.304C>A	p.Pro102Thr	missense_variant	Exon 3 of 16	1	NM_012387.3	ENSP00000364597.4		Q9UM07
PADI4	ENST00000375453.5 link	c.304C>A	p.Pro102Thr	missense_variant	Exon 3 of 4	2		ENSP00000364602.1		B1AQ67

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1666

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00321

Gnomad AMI

AF:

0.0286

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00763

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0173

Gnomad OTH

AF:

0.0163

GnomAD2 exomes

AF:

0.0108

AC:

2715

AN:

251444

AF XY:

0.0109

show subpopulations

Gnomad AFR exome

AF:

0.00344

Gnomad AMR exome

AF:

0.0103

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00744

Gnomad NFE exome

AF:

0.0175

Gnomad OTH exome

AF:

0.0135

GnomAD4 exome

AF:

0.0153

AC:

22337

AN:

1460290

Hom.:

225

Cov.:

AF XY:

0.0149

AC XY:

10800

AN XY:

726548

show subpopulations

African (AFR)

AF:

0.00236

AC:

AN:

33466

American (AMR)

AF:

0.0110

AC:

492

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000804

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00191

AC:

165

AN:

86244

European-Finnish (FIN)

AF:

0.00754

AC:

403

AN:

53414

Middle Eastern (MID)

AF:

0.00382

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0183

AC:

20268

AN:

1110512

Other (OTH)

AF:

0.0147

AC:

885

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

950

1900

2851

3801

4751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0109

AC:

1666

AN:

152240

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

780

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00320

AC:

133

AN:

41556

American (AMR)

AF:

0.0133

AC:

203

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00145

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00763

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0173

AC:

1178

AN:

68010

Other (OTH)

AF:

0.0161

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

174

262

349

436

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0142

Hom.:

Bravo

AF:

0.0112

TwinsUK

AF:

0.0173

AC:

ALSPAC

AF:

0.0148

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0197

AC:

169

ExAC

AF:

0.0106

AC:

1283

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0172

EpiControl

AF:

0.0183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.5

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0047

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;L

PhyloP100

-1.4

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.010

Sift

Benign

0.093

T;D

Sift4G

Benign

0.79

T;T

Polyphen

0.0060

.;B

Vest4

0.12

MPC

0.12

ClinPred

0.0099

GERP RS

-9.5

Varity_R

0.10

gMVP

0.13

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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rs34309058

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