rs34309058

Variant names:

• chr1-17333973-C-A
• rs34309058
• NM_012387.3:c.304C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-17333973-C-A
• chr1-17333973-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_012387.3(PADI4):​c.304C>A​(p.Pro102Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,612,530 control chromosomes in the GnomAD database, including 241 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.011 (16 hom., cov: 30)
  • Exomes 𝑓: 0.015 (225 hom.)
• Consequence: PADI4 NM_012387.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029465556).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0109 (1666/152240) while in subpopulation NFE AF = 0.0173 (1178/68010). AF 95% confidence interval is 0.0165. There are 16 homozygotes in GnomAd4. There are 780 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012387.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI4	NM_012387.3	MANE Select	c.304C>A	p.Pro102Thr	missense	Exon 3 of 16	NP_036519.2	Q9UM07

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI4	ENST00000375448.4	TSL:1 MANE Select	c.304C>A	p.Pro102Thr	missense	Exon 3 of 16	ENSP00000364597.4	Q9UM07
	PADI4	ENST00000375453.5	TSL:2	c.304C>A	p.Pro102Thr	missense	Exon 3 of 4	ENSP00000364602.1	B1AQ67

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1666 AN: 152122 Hom.: 16 Cov.: 30

Gnomad AFR AF: 0.00321

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00763

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0173

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.0108 AC: 2715 AN: 251444 AF XY: 0.0109

Gnomad AFR exome AF: 0.00344

Gnomad AMR exome AF: 0.0103

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00744

Gnomad NFE exome AF: 0.0175

Gnomad OTH exome AF: 0.0135

GnomAD4 exome AF: 0.0153 AC: 22337 AN: 1460290 Hom.: 225 Cov.: 28 AF XY: 0.0149 AC XY: 10800 AN XY: 726548

African (AFR) AF: 0.00236 AC: 79 AN: 33466

American (AMR) AF: 0.0110 AC: 492 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000804 AC: 21 AN: 26130

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00191 AC: 165 AN: 86244

European-Finnish (FIN) AF: 0.00754 AC: 403 AN: 53414

Middle Eastern (MID) AF: 0.00382 AC: 22 AN: 5766

European-Non Finnish (NFE) AF: 0.0183 AC: 20268 AN: 1110512

Other (OTH) AF: 0.0147 AC: 885 AN: 60340

GnomAD4 genome AF: 0.0109 AC: 1666 AN: 152240 Hom.: 16 Cov.: 30 AF XY: 0.0105 AC XY: 780 AN XY: 74432

African (AFR) AF: 0.00320 AC: 133 AN: 41556

American (AMR) AF: 0.0133 AC: 203 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4816

European-Finnish (FIN) AF: 0.00763 AC: 81 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0173 AC: 1178 AN: 68010

Other (OTH) AF: 0.0161 AC: 34 AN: 2112

Alfa AF: 0.0142 Hom.: 68

Bravo AF: 0.0112

TwinsUK AF: 0.0173 AC: 64

ALSPAC AF: 0.0148 AC: 57

ESP6500AA AF: 0.00340 AC: 15

ESP6500EA AF: 0.0197 AC: 169

ExAC AF: 0.0106 AC: 1283

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0172

EpiControl AF: 0.0183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.5
DANN	Benign	0.85
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0047	N
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-1.4
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.010
Sift	Benign	0.093	T
Sift4G	Benign	0.79	T
Polyphen		0.0060	B
Vest4		0.12
MPC		0.12
ClinPred		0.0099	T
GERP RS		-9.5
Varity_R		0.10
gMVP		0.13
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs34309058; hg19: chr1-17660468; COSMIC: COSV99080970;