Genetic Variant NM_016233.2:c.347-475T>C (chr1-17265184-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016233.2(PADI3):c.347-475T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0388 in 152,082 control chromosomes in the GnomAD database, including 177 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 0.039 ( 177 hom., cov: 32)

Consequence

PADI3
NM_016233.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.71

Publications

4 publications found

Variant links:

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

PADI3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
PADI3	NM_016233.2 link	c.347-475T>C	intron_variant	Intron 3 of 15	ENST00000375460.3	NP_057317.2
PADI3	XM_011541571.3 link	c.233-475T>C	intron_variant	Intron 3 of 15		XP_011539873.1
PADI3	XM_011541572.3 link	c.347-475T>C	intron_variant	Intron 3 of 11		XP_011539874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI3	ENST00000375460.3 link	c.347-475T>C		intron_variant	Intron 3 of 15	1	NM_016233.2	ENSP00000364609.3		Q9ULW8

Frequencies

GnomAD3 genomes

AF:

0.0387

AC:

5882

AN:

151968

Hom.:

174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0100

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0248

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.0794

Gnomad FIN

AF:

0.0442

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0511

Gnomad OTH

AF:

0.0344

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

GnomAD4 genome

AF:

0.0388

AC:

5899

AN:

152082

Hom.:

177

Cov.:

AF XY:

0.0391

AC XY:

2907

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00998

AC:

414

AN:

41494

American (AMR)

AF:

0.0248

AC:

379

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0210

AC:

AN:

3470

East Asian (EAS)

AF:

0.116

AC:

599

AN:

5152

South Asian (SAS)

AF:

0.0797

AC:

383

AN:

4806

European-Finnish (FIN)

AF:

0.0442

AC:

468

AN:

10588

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0511

AC:

3476

AN:

67972

Other (OTH)

AF:

0.0412

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

271

543

814

1086

1357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0319

Hom.:

Bravo

AF:

0.0352

Asia WGS

AF:

0.0990

AC:

343

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.054

(source)

DANN

Benign

0.67

PhyloP100

-2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over