Genetic Variant PADI3:c.1307+806A>T (chr1-17275592-A-T) – 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.1307+806A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,096 control chromosomes in the GnomAD database, including 13,652 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 0.40 ( 13652 hom., cov: 32)

Consequence

PADI3
NM_016233.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.491

Publications

5 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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
PADI3	NM_016233.2 link	c.1307+806A>T	intron_variant	Intron 11 of 15	ENST00000375460.3	NP_057317.2
PADI3	XM_011541571.3 link	c.1193+806A>T	intron_variant	Intron 11 of 15		XP_011539873.1
PADI3	XM_017001463.2 link	c.770+806A>T	intron_variant	Intron 8 of 12		XP_016856952.1
PADI3	XM_011541572.3 link	c.1156-927A>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 link	c.1307+806A>T		intron_variant	Intron 11 of 15	1	NM_016233.2	ENSP00000364609.3		Q9ULW8

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

60376

AN:

151978

Hom.:

13657

Cov.:

show subpopulations

Gnomad AFR

AF:

0.167

Gnomad AMI

AF:

0.391

Gnomad AMR

AF:

0.463

Gnomad ASJ

AF:

0.600

Gnomad EAS

AF:

0.635

Gnomad SAS

AF:

0.488

Gnomad FIN

AF:

0.473

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.474

Gnomad OTH

AF:

0.430

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

GnomAD4 genome

AF:

0.397

AC:

60360

AN:

152096

Hom.:

13652

Cov.:

AF XY:

0.399

AC XY:

29666

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.167

AC:

6914

AN:

41518

American (AMR)

AF:

0.463

AC:

7070

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.600

AC:

2083

AN:

3472

East Asian (EAS)

AF:

0.635

AC:

3288

AN:

5180

South Asian (SAS)

AF:

0.489

AC:

2356

AN:

4818

European-Finnish (FIN)

AF:

0.473

AC:

4994

AN:

10552

Middle Eastern (MID)

AF:

0.554

AC:

163

AN:

294

European-Non Finnish (NFE)

AF:

0.474

AC:

32234

AN:

67964

Other (OTH)

AF:

0.427

AC:

901

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1656

3312

4967

6623

8279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

584

1168

1752

2336

2920

<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:

0.290

Hom.:

822

Bravo

AF:

0.387

Asia WGS

AF:

0.474

AC:

1644

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.2

(source)

DANN

Benign

0.86

PhyloP100

-0.49

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