1-17249150-A-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_016233.2(PADI3):c.13A>C(p.Arg5=) 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 (★).

• Frequency:
  • Genomes: 𝑓 0.071 (473 hom., cov: 32)
  • Exomes 𝑓: 0.085 (6192 hom.)
• Consequence: PADI3 NM_016233.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.27

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]

ACMG classification

Verdict is Benign. Variant got -15 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 criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
PADI3	NM_016233.2	c.13A>C	p.Arg5=	synonymous_variant	1/16	ENST00000375460.3
PADI3	XM_011541572.3	c.13A>C	p.Arg5=	synonymous_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI3	ENST00000375460.3	c.13A>C	p.Arg5=	synonymous_variant	1/16	1	NM_016233.2	P1

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10876 AN: 152124 Hom.: 472 Cov.: 32

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

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.: 31 AF XY: 0.0877 AC XY: 63800 AN XY: 727168

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.: 32 AF XY: 0.0741 AC XY: 5518 AN XY: 74434

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: criteria provided, single submitter

Submissions by phenotype

PADI3-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 15, 2019

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	13
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

Other links and lift over

dbSNP: rs3763589; hg19: chr1-17575645; COSMIC: COSV64934190; COSMIC: COSV64934190;