1-17331096-G-A

Variant names:

• chr1-17331096-G-A
• rs772051391
• NM_012387.3:c.220G>A

Variant summary

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

The NM_012387.3(PADI4):​c.220G>A​(p.Val74Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V74L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PADI4 NM_012387.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295
• Publications: 0 publications found

Genes affected

PADI4 (HGNC:18368): (peptidyl arginine deiminase 4) This gene is a member of a gene family which encodes enzymes responsible for the conversion of arginine residues to citrulline residues. This gene may play a role in granulocyte and macrophage development leading to inflammation and immune response. [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=0.1194157).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3	c.220G>A	p.Val74Ile	missense_variant	Exon 2 of 16	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.220G>A	p.Val74Ile	missense_variant	Exon 2 of 16	1	NM_012387.3	ENSP00000364597.4
PADI4	ENST00000375453.5	c.220G>A	p.Val74Ile	missense_variant	Exon 2 of 4	2		ENSP00000364602.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460224 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 726370

African (AFR) AF: 0.00 AC: 0 AN: 33396

American (AMR) AF: 0.00 AC: 0 AN: 44440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39592

South Asian (SAS) AF: 0.00 AC: 0 AN: 85936

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111284

Other (OTH) AF: 0.00 AC: 0 AN: 60342

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.4
DANN	Benign	0.91
DEOGEN2	Benign	0.0084	T;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.10	N
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	.;L
PhyloP100		0.29
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.30	N;N
REVEL	Benign	0.038
Sift	Benign	0.16	T;T
Sift4G	Benign	0.098	T;T
Polyphen		0.27	.;B
Vest4		0.089
MutPred		0.41		Loss of catalytic residue at V74 (P = 0.0132);Loss of catalytic residue at V74 (P = 0.0132);
MVP		0.15
MPC		0.15
ClinPred		0.21	T
GERP RS		2.3
Varity_R		0.089
gMVP		0.079
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs772051391; hg19: chr1-17657591;