chr1-17249833-T-C

Position:

• chr1-17249833-T-C

Variant summary

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

The NM_016233.2(PADI3):​c.92+604T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,100 control chromosomes in the GnomAD database, including 18,300 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 0.49 (18300 hom., cov: 33)
• Consequence: PADI3 NM_016233.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI3	NM_016233.2	c.92+604T>C		intron_variant		ENST00000375460.3	NP_057317.2
PADI3	XM_011541572.3	c.92+604T>C		intron_variant			XP_011539874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI3	ENST00000375460.3	c.92+604T>C		intron_variant		1	NM_016233.2	ENSP00000364609.3

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73780 AN: 151982 Hom.: 18260 Cov.: 33

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.486 AC: 73872 AN: 152100 Hom.: 18300 Cov.: 33 AF XY: 0.485 AC XY: 36088 AN XY: 74344

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.463

Alfa AF: 0.455 Hom.: 32389

Bravo AF: 0.483

Asia WGS AF: 0.547 AC: 1901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.32
DANN	Benign	0.44

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: rs2977227; hg19: chr1-17576328;