rs12037558

Positions:

• chr1-17281858-G-A
• chr1-17281858-G-C

Variant summary

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

The ENST00000375460.3(PADI3):​c.1762-988G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,098 control chromosomes in the GnomAD database, including 11,540 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 0.36 (11540 hom., cov: 32)
• Consequence: PADI3 ENST00000375460.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI3	NM_016233.2	c.1762-988G>A		intron_variant		ENST00000375460.3	NP_057317.2
PADI3	XM_011541571.3	c.1648-988G>A		intron_variant			XP_011539873.1
PADI3	XM_017001463.2	c.1225-988G>A		intron_variant			XP_016856952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI3	ENST00000375460.3	c.1762-988G>A		intron_variant		1	NM_016233.2	ENSP00000364609	P1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54428 AN: 151978 Hom.: 11543 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.358 AC: 54410 AN: 152098 Hom.: 11540 Cov.: 32 AF XY: 0.361 AC XY: 26840 AN XY: 74352

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.637

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.376

Alfa AF: 0.260 Hom.: 737

Bravo AF: 0.346

Asia WGS AF: 0.466 AC: 1615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.75

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: rs12037558; hg19: chr1-17608353; COSMIC: COSV64934271; COSMIC: COSV64934271;