chr1-17273974-C-T

Variant names:

• chr1-17273974-C-T
• rs2977296
• NM_016233.2:c.1155+527C>T

Variant summary

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

The NM_016233.2(PADI3):​c.1155+527C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 151,784 control chromosomes in the GnomAD database, including 8,618 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 0.33 (8618 hom., cov: 32)
• Consequence: PADI3 NM_016233.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 4 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: G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI3	NM_016233.2	c.1155+527C>T		intron_variant	Intron 10 of 15	ENST00000375460.3	NP_057317.2
PADI3	XM_011541571.3	c.1041+527C>T		intron_variant	Intron 10 of 15		XP_011539873.1
PADI3	XM_017001463.2	c.618+527C>T		intron_variant	Intron 7 of 12		XP_016856952.1
PADI3	XM_011541572.3	c.1155+527C>T		intron_variant	Intron 10 of 11		XP_011539874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI3	ENST00000375460.3	c.1155+527C>T		intron_variant	Intron 10 of 15	1	NM_016233.2	ENSP00000364609.3

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50367 AN: 151666 Hom.: 8594 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.332 AC: 50447 AN: 151784 Hom.: 8618 Cov.: 32 AF XY: 0.331 AC XY: 24535 AN XY: 74148

African (AFR) AF: 0.378 AC: 15639 AN: 41358

American (AMR) AF: 0.277 AC: 4225 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 916 AN: 3472

East Asian (EAS) AF: 0.170 AC: 878 AN: 5158

South Asian (SAS) AF: 0.209 AC: 1003 AN: 4808

European-Finnish (FIN) AF: 0.363 AC: 3821 AN: 10530

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.335 AC: 22754 AN: 67904

Other (OTH) AF: 0.326 AC: 686 AN: 2106

Alfa AF: 0.210 Hom.: 479

Bravo AF: 0.329

Asia WGS AF: 0.239 AC: 834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.43
PhyloP100		-1.4
Mutation Taster		=100/0	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: rs2977296; hg19: chr1-17600469;