1-17222291-G-A

Variant names:

• chr1-17222291-G-A
• NM_013358.3:c.94G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013358.3(PADI1):​c.94G>A​(p.Asp32Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PADI1 NM_013358.3 missense, splice_region
• Scores: Splicing: ADA: 0.004523
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24384618).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI1	NM_013358.3	c.94G>A	p.Asp32Asn	missense_variant, splice_region_variant	Exon 2 of 16	ENST00000375471.5	NP_037490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI1	ENST00000375471.5	c.94G>A	p.Asp32Asn	missense_variant, splice_region_variant	Exon 2 of 16	1	NM_013358.3	ENSP00000364620.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.94G>A (p.D32N) alteration is located in exon 2 (coding exon 2) of the PADI1 gene. This alteration results from a G to A substitution at nucleotide position 94, causing the aspartic acid (D) at amino acid position 32 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.58	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.4
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.059
Sift	Benign	0.21	T
Sift4G	Benign	0.16	T
Polyphen		0.37	B
Vest4		0.30
MutPred		0.55		Gain of methylation at K35 (P = 0.0523);
MVP		0.33
MPC		0.17
ClinPred		0.63	D
GERP RS		2.8
Varity_R		0.079
gMVP		0.25
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0045
dbscSNV1_RF	Benign	0.044
SpliceAI score (max)		0.040		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

hg19: chr1-17548786;