1-17226078-A-G

Position:

• chr1-17226078-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_013358.3(PADI1):​c.572A>G​(p.Asp191Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00646 in 1,614,148 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (53 hom.)
• Consequence: PADI1 NM_013358.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.07

Genes affected

PADI1 (HGNC:18367): (peptidyl arginine deiminase 1) 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 I enzyme is involved in the late stages of epidermal differentiation, where it deiminates filaggrin and keratin K1, which maintains hydration of the stratum corneum, and hence the cutaneous barrier function. This enzyme may also play a role in hair follicle formation. This gene exists in a cluster with four other paralogous genes. [provided by RefSeq, Jul 2008]

PADI1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0056008697).
• BP6: Variant 1-17226078-A-G is Benign according to our data. Variant chr1-17226078-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 773391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI1	NM_013358.3	c.572A>G	p.Asp191Gly	missense_variant	6/16	ENST00000375471.5	NP_037490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI1	ENST00000375471.5	c.572A>G	p.Asp191Gly	missense_variant	6/16	1	NM_013358.3	ENSP00000364620.4
PADI1	ENST00000483501.1	n.433A>G		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.00417 AC: 634 AN: 152158 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00720

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00431 AC: 1083 AN: 251476 Hom.: 7 AF XY: 0.00455 AC XY: 618 AN XY: 135910

Gnomad AFR exome AF: 0.000984

Gnomad AMR exome AF: 0.000809

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00444

Gnomad FIN exome AF: 0.00120

Gnomad NFE exome AF: 0.00750

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00670 AC: 9790 AN: 1461872 Hom.: 53 Cov.: 32 AF XY: 0.00659 AC XY: 4790 AN XY: 727238

Gnomad4 AFR exome AF: 0.000836

Gnomad4 AMR exome AF: 0.000984

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00478

Gnomad4 FIN exome AF: 0.00150

Gnomad4 NFE exome AF: 0.00800

Gnomad4 OTH exome AF: 0.00522

GnomAD4 genome AF: 0.00416 AC: 634 AN: 152276 Hom.: 4 Cov.: 32 AF XY: 0.00391 AC XY: 291 AN XY: 74464

Gnomad4 AFR AF: 0.00132

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.00170

Gnomad4 NFE AF: 0.00720

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00619 Hom.: 6

Bravo AF: 0.00407

TwinsUK AF: 0.00917 AC: 34

ALSPAC AF: 0.00778 AC: 30

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00698 AC: 60

ExAC AF: 0.00492 AC: 597

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00687

EpiControl AF: 0.00652

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 15, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.36	N
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.0056	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.041
Sift	Benign	0.43	T
Sift4G	Benign	0.38	T
Polyphen		0.15	B
Vest4		0.39
MVP		0.35
MPC		0.22
ClinPred		0.021	T
GERP RS		4.9
Varity_R		0.18
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs150923523; hg19: chr1-17552573;