1-17278206-G-C

Position:

• chr1-17278206-G-C

Variant summary

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

The NM_016233.2(PADI3):​c.1555+1330G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 152,124 control chromosomes in the GnomAD database, including 24,396 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 0.56 (24396 hom., cov: 34)
• Consequence: PADI3 NM_016233.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI3	NM_016233.2	c.1555+1330G>C		intron_variant		ENST00000375460.3
PADI3	XM_011541571.3	c.1441+1330G>C		intron_variant
PADI3	XM_017001463.2	c.1018+1330G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI3	ENST00000375460.3	c.1555+1330G>C		intron_variant		1	NM_016233.2	P1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 85046 AN: 152006 Hom.: 24341 Cov.: 34

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.560 AC: 85165 AN: 152124 Hom.: 24396 Cov.: 34 AF XY: 0.559 AC XY: 41536 AN XY: 74346

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.538

Alfa AF: 0.548 Hom.: 2884

Bravo AF: 0.564

Asia WGS AF: 0.518 AC: 1805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.50

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: rs2977299; hg19: chr1-17604701;