rs3003429

Variant names:

• chr1-17265184-T-C
• rs3003429
• NM_016233.2:c.347-475T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016233.2(PADI3):​c.347-475T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0388 in 152,082 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.039 (177 hom., cov: 32)
• Consequence: PADI3 NM_016233.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI3	NM_016233.2	c.347-475T>C		intron_variant	Intron 3 of 15	ENST00000375460.3	NP_057317.2
PADI3	XM_011541571.3	c.233-475T>C		intron_variant	Intron 3 of 15		XP_011539873.1
PADI3	XM_011541572.3	c.347-475T>C		intron_variant	Intron 3 of 11		XP_011539874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI3	ENST00000375460.3	c.347-475T>C		intron_variant	Intron 3 of 15	1	NM_016233.2	ENSP00000364609.3

Frequencies

GnomAD3 genomes AF: 0.0387 AC: 5882 AN: 151968 Hom.: 174 Cov.: 32

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0794

Gnomad FIN AF: 0.0442

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0511

Gnomad OTH AF: 0.0344

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0388 AC: 5899 AN: 152082 Hom.: 177 Cov.: 32 AF XY: 0.0391 AC XY: 2907 AN XY: 74354

Gnomad4 AFR AF: 0.00998

Gnomad4 AMR AF: 0.0248

Gnomad4 ASJ AF: 0.0210

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.0797

Gnomad4 FIN AF: 0.0442

Gnomad4 NFE AF: 0.0511

Gnomad4 OTH AF: 0.0412

Alfa AF: 0.0417 Hom.: 31

Bravo AF: 0.0352

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.054
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3003429; hg19: chr1-17591679;