Genetic Variant NM_016233.2:c.13A>C (chr1-17249150-A-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_016233.2(PADI3):c.13A>C(p.Arg5Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0833 in 1,613,938 control chromosomes in the GnomAD database, including 6,665 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.071 ( 473 hom., cov: 32)

Exomes 𝑓: 0.085 ( 6192 hom. )

Consequence

PADI3
NM_016233.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.27

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 1-17249150-A-C is Benign according to our data. Variant chr1-17249150-A-C is described in ClinVar as [Benign]. Clinvar id is 3060112.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=3.27 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI3	NM_016233.2 link	c.13A>C	p.Arg5Arg	synonymous_variant	Exon 1 of 16	ENST00000375460.3	NP_057317.2
PADI3	XM_011541572.3 link	c.13A>C	p.Arg5Arg	synonymous_variant	Exon 1 of 12		XP_011539874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI3	ENST00000375460.3 link	c.13A>C	p.Arg5Arg	synonymous_variant	Exon 1 of 16	1	NM_016233.2	ENSP00000364609.3		Q9ULW8

Frequencies

GnomAD3 genomes

AF:

0.0715

AC:

10876

AN:

152124

Hom.:

472

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0370

Gnomad AMI

AF:

0.0363

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.0565

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.0592

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0726

Gnomad OTH

AF:

0.0713

GnomAD3 exomes

AF:

0.0972

AC:

24445

AN:

251410

Hom.:

1548

AF XY:

0.102

AC XY:

13811

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0366

Gnomad AMR exome

AF:

0.125

Gnomad ASJ exome

AF:

0.0560

Gnomad EAS exome

AF:

0.158

Gnomad SAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.0575

Gnomad NFE exome

AF:

0.0730

Gnomad OTH exome

AF:

0.0895

GnomAD4 exome

AF:

0.0845

AC:

123556

AN:

1461696

Hom.:

6192

Cov.:

AF XY:

0.0877

AC XY:

63800

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.0353

Gnomad4 AMR exome

AF:

0.119

Gnomad4 ASJ exome

AF:

0.0599

Gnomad4 EAS exome

AF:

0.154

Gnomad4 SAS exome

AF:

0.191

Gnomad4 FIN exome

AF:

0.0568

Gnomad4 NFE exome

AF:

0.0756

Gnomad4 OTH exome

AF:

0.0880

GnomAD4 genome

AF:

0.0715

AC:

10883

AN:

152242

Hom.:

473

Cov.:

AF XY:

0.0741

AC XY:

5518

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0369

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.0565

Gnomad4 EAS

AF:

0.155

Gnomad4 SAS

AF:

0.192

Gnomad4 FIN

AF:

0.0592

Gnomad4 NFE

AF:

0.0726

Gnomad4 OTH

AF:

0.0729

Alfa

AF:

0.0698

Hom.:

233

Bravo

AF:

0.0721

Asia WGS

AF:

0.166

AC:

578

AN:

3478

EpiCase

AF:

0.0763

EpiControl

AF:

0.0768

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PADI3-related disorder

Benign:1

Mar 15, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.86

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