chr1-17249150-A-C

Variant names:

• chr1-17249150-A-C
• rs3763589
• NM_016233.2:c.13A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

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
• Clinical Significance: Benign no assertion criteria provided 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

Our verdict: Benign. The variant received -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	c.13A>C	p.Arg5Arg	synonymous_variant	Exon 1 of 16	ENST00000375460.3	NP_057317.2
PADI3	XM_011541572.3	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	c.13A>C	p.Arg5Arg	synonymous_variant	Exon 1 of 16	1	NM_016233.2	ENSP00000364609.3

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

GnomAD2 exomes AF: 0.0972 AC: 24445 AN: 251410 AF XY: 0.102

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 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 AC: 1182 AN: 33478

Gnomad4 AMR exome AF: 0.119 AC: 5305 AN: 44722

Gnomad4 ASJ exome AF: 0.0599 AC: 1564 AN: 26132

Gnomad4 EAS exome AF: 0.154 AC: 6126 AN: 39700

Gnomad4 SAS exome AF: 0.191 AC: 16480 AN: 86248

Gnomad4 FIN exome AF: 0.0568 AC: 3034 AN: 53416

Gnomad4 NFE exome AF: 0.0756 AC: 84094 AN: 1111836

Gnomad4 Remaining exome AF: 0.0880 AC: 5315 AN: 60396

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 AC: 0.0368971 AN: 0.0368971

Gnomad4 AMR AF: 0.108 AC: 0.108292 AN: 0.108292

Gnomad4 ASJ AF: 0.0565 AC: 0.0564841 AN: 0.0564841

Gnomad4 EAS AF: 0.155 AC: 0.154517 AN: 0.154517

Gnomad4 SAS AF: 0.192 AC: 0.192499 AN: 0.192499

Gnomad4 FIN AF: 0.0592 AC: 0.0592453 AN: 0.0592453

Gnomad4 NFE AF: 0.0726 AC: 0.0726129 AN: 0.0726129

Gnomad4 OTH AF: 0.0729 AC: 0.0729167 AN: 0.0729167

Alfa AF: 0.0712 Hom.: 390

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

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	13
DANN	Benign	0.86
Mutation Taster		=95/5	polymorphism (auto)

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;