Genetic Variant PADI3:c.92+604T>C (chr1-17249833-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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.942

Publications

8 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=-0.93).

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 rank	MANE	Protein	UniProt
PADI3	NM_016233.2 link	c.92+604T>C		intron_variant	Intron 1 of 15	ENST00000375460.3	NP_057317.2
PADI3	XM_011541572.3 link	c.92+604T>C		intron_variant	Intron 1 of 11		XP_011539874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI3	ENST00000375460.3 link	c.92+604T>C		intron_variant	Intron 1 of 15	1	NM_016233.2	ENSP00000364609.3		Q9ULW8

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73780

AN:

151982

Hom.:

18260

Cov.:

show subpopulations

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.:

AF XY:

0.485

AC XY:

36088

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.579

AC:

23988

AN:

41462

American (AMR)

AF:

0.411

AC:

6280

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.385

AC:

1335

AN:

3464

East Asian (EAS)

AF:

0.426

AC:

2203

AN:

5170

South Asian (SAS)

AF:

0.558

AC:

2688

AN:

4816

European-Finnish (FIN)

AF:

0.425

AC:

4501

AN:

10590

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.460

AC:

31263

AN:

68000

Other (OTH)

AF:

0.463

AC:

979

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1949

3898

5846

7795

9744

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

662

1324

1986

2648

3310

<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:

0.462

Hom.:

51278

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

(source)

DANN

Benign

0.44

PhyloP100

-0.94

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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