Variant 1-17266737-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_016233.2(PADI3):c.427C>T(p.Pro143Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00241 in 1,613,986 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 10 hom. )

Consequence

PADI3
NM_016233.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.32

Variant links:

Genes affected

PADI3 (HGNC:18337): (peptidyl arginine deiminase 3) This gene encodes a member of the peptidyl arginine deiminase family of enzymes, which catalyze the post-translational deimination of proteins by converting arginine residues into citrullines in the presence of calcium ions. The family members have distinct substrate specificities and tissue-specific expression patterns. The type III enzyme modulates hair structural proteins, such as filaggrin in the hair follicle and trichohyalin in the inner root sheath, during hair follicle formation. Together with the type I enzyme, this enzyme may also play a role in terminal differentiation of the epidermis. This gene exists in a cluster with four other paralogous genes. [provided by RefSeq, Jul 2008]

PADI3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063054264).

BP6

Variant 1-17266737-C-T is Benign according to our data. Variant chr1-17266737-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638392.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PADI3	NM_016233.2 linkuse as main transcript	c.427C>T	p.Pro143Ser	missense_variant	5/16	ENST00000375460.3
PADI3	XM_011541571.3 linkuse as main transcript	c.313C>T	p.Pro105Ser	missense_variant	5/16
PADI3	XM_011541572.3 linkuse as main transcript	c.427C>T	p.Pro143Ser	missense_variant	5/12
PADI3	XM_017001463.2 linkuse as main transcript	c.-111C>T		5_prime_UTR_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI3	ENST00000375460.3 linkuse as main transcript	c.427C>T	p.Pro143Ser	missense_variant	5/16	1	NM_016233.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00200

AC:

305

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00235

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00206

AC:

516

AN:

250786

Hom.:

AF XY:

0.00204

AC XY:

277

AN XY:

135602

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00387

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000602

Gnomad NFE exome

AF:

0.00269

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00245

AC:

3583

AN:

1461732

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

1787

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.00400

Gnomad4 ASJ exome

AF:

0.00406

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.000805

Gnomad4 NFE exome

AF:

0.00277

Gnomad4 OTH exome

AF:

0.00237

GnomAD4 genome

AF:

0.00200

AC:

305

AN:

152254

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

137

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00588

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00235

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00279

Hom.:

Bravo

AF:

0.00260

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00201

AC:

244

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00436

EpiControl

AF:

0.00367

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

PADI3: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.099

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.016

MetaRNN

Benign

0.0063

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-6.0

REVEL

Benign

0.21

Sift

Benign

0.056

Sift4G

Uncertain

0.029

Polyphen

0.98

Vest4

0.36

MVP

0.50

MPC

0.18

ClinPred

0.033

GERP RS

4.2

Varity_R

0.54

gMVP

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over