1-17333973-C-G

Position:

• chr1-17333973-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012387.3(PADI4):​c.304C>G​(p.Pro102Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,612,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. P102T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: PADI4 NM_012387.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.083826035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI4	NM_012387.3	c.304C>G	p.Pro102Ala	missense_variant	3/16	ENST00000375448.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI4	ENST00000375448.4	c.304C>G	p.Pro102Ala	missense_variant	3/16	1	NM_012387.3	P1
PADI4	ENST00000375453.5	c.304C>G	p.Pro102Ala	missense_variant	3/4	2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152122 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1460680 Hom.: 0 Cov.: 28 AF XY: 0.0000165 AC XY: 12 AN XY: 726732

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152122 Hom.: 0 Cov.: 30 AF XY: 0.0000404 AC XY: 3 AN XY: 74304

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.8
DANN	Benign	0.62
DEOGEN2	Benign	0.018	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0050	N
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.032
Sift	Benign	0.17	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.0010	.;B
Vest4		0.14
MutPred		0.49		Loss of glycosylation at P102 (P = 0.0225);Loss of glycosylation at P102 (P = 0.0225);
MVP		0.030
MPC		0.11
ClinPred		0.063	T
GERP RS		-9.5
Varity_R		0.13
gMVP		0.069

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

Publications

LitVar

Other links and lift over

dbSNP: rs34309058; hg19: chr1-17660468;