rs144944758

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_016233.2(PADI3):c.1813C>A(p.Pro605Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000782 in 1,613,926 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00081 ( 1 hom. )

Consequence

PADI3
NM_016233.2 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.69

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 Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.928

PP5

Variant 1-17282897-C-A is Pathogenic according to our data. Variant chr1-17282897-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 374869.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-17282897-C-A is described in UniProt as null. Variant chr1-17282897-C-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PADI3	NM_016233.2 linkuse as main transcript	c.1813C>A	p.Pro605Thr	missense_variant	16/16	ENST00000375460.3
PADI3	XM_011541571.3 linkuse as main transcript	c.1699C>A	p.Pro567Thr	missense_variant	16/16
PADI3	XM_017001463.2 linkuse as main transcript	c.1276C>A	p.Pro426Thr	missense_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI3	ENST00000375460.3 linkuse as main transcript	c.1813C>A	p.Pro605Thr	missense_variant	16/16	1	NM_016233.2	P1

Frequencies

GnomAD3 genomes

AF:

0.000558

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00115

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000443

AC:

111

AN:

250596

Hom.:

AF XY:

0.000436

AC XY:

AN XY:

135472

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000901

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000805

AC:

1177

AN:

1461708

Hom.:

Cov.:

AF XY:

0.000773

AC XY:

562

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00101

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.000558

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00115

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00103

Hom.:

Bravo

AF:

0.000563

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000428

AC:

EpiCase

AF:

0.000818

EpiControl

AF:

0.000830

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Uncombable hair syndrome 1

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 07, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.050

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.039

MetaRNN

Pathogenic

0.93

MetaSVM

Uncertain

-0.11

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-7.8

REVEL

Pathogenic

0.75

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.96

MVP

0.74

MPC

0.54

ClinPred

0.77

GERP RS

4.2

Varity_R

0.93

gMVP

0.84

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