1-17281858-G-A

Variant names:

• chr1-17281858-G-A
• rs12037558
• NM_016233.2:c.1762-988G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016233.2(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 NM_016233.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• Publications: 5 publications found

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]

PADI3 Gene-Disease associations (from GenCC):

• uncombable hair syndrome 1

  Inheritance: AR, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Laboratory for Molecular Medicine, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• uncombable hair syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016233.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI3	NM_016233.2	MANE Select	c.1762-988G>A		intron	N/A	NP_057317.2	Q9ULW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI3	ENST00000375460.3	TSL:1 MANE Select	c.1762-988G>A		intron	N/A	ENSP00000364609.3	Q9ULW8

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

African (AFR) AF: 0.120 AC: 4993 AN: 41516

American (AMR) AF: 0.420 AC: 6430 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1757 AN: 3464

East Asian (EAS) AF: 0.637 AC: 3278 AN: 5142

South Asian (SAS) AF: 0.476 AC: 2298 AN: 4826

European-Finnish (FIN) AF: 0.446 AC: 4719 AN: 10570

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.437 AC: 29693 AN: 67960

Other (OTH) AF: 0.376 AC: 794 AN: 2114

Alfa AF: 0.348 Hom.: 2606

Bravo AF: 0.346

Asia WGS AF: 0.466 AC: 1615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.75
PhyloP100		-0.20
Mutation Taster		=99/1	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

Other links and lift over

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