rs35809521

Variant names:

• chr1-17331112-C-G
• rs35809521
• NM_012387.3:c.236C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-17331112-C-G
• chr1-17331112-C-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_012387.3(PADI4):​c.236C>G​(p.Thr79Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000298 in 1,611,980 control chromosomes in the GnomAD database, including 5 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 Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T79M) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00029 (5 hom.)
• Consequence: PADI4 NM_012387.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.65
• 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0062113404).
• BP6: Variant 1-17331112-C-G is Benign according to our data. Variant chr1-17331112-C-G is described in ClinVar as Benign. ClinVar VariationId is 3048532.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 5 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.236C>G	p.Thr79Arg	missense	Exon 2 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.236C>G	p.Thr79Arg	missense	Exon 2 of 16	ENSP00000364597.4	Q9UM07
	PADI4	ENST00000375453.5	TSL:2	c.236C>G	p.Thr79Arg	missense	Exon 2 of 4	ENSP00000364602.1	B1AQ67

Frequencies

GnomAD3 genomes AF: 0.000421 AC: 64 AN: 152144 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0122

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000962 AC: 239 AN: 248398 AF XY: 0.000879

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000298

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000286 AC: 417 AN: 1459718 Hom.: 5 Cov.: 37 AF XY: 0.000273 AC XY: 198 AN XY: 726112

African (AFR) AF: 0.00 AC: 0 AN: 33334

American (AMR) AF: 0.0000226 AC: 1 AN: 44290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00989 AC: 391 AN: 39540

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5760

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111114

Other (OTH) AF: 0.000348 AC: 21 AN: 60330

GnomAD4 genome AF: 0.000420 AC: 64 AN: 152262 Hom.: 0 Cov.: 33 AF XY: 0.000443 AC XY: 33 AN XY: 74434

African (AFR) AF: 0.00 AC: 0 AN: 41556

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0122 AC: 63 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000213 Hom.: 9

Bravo AF: 0.000548

ExAC AF: 0.000857 AC: 104

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PADI4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.021
DANN	Benign	0.26
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0053	N
MetaRNN	Benign	0.0062	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.77	N
PhyloP100		-1.7
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.014
Sift	Benign	0.36	T
Sift4G	Benign	0.83	T
Polyphen		0.0020	B
Vest4		0.12
MutPred		0.24		Loss of glycosylation at T79 (P = 0.0457)
MVP		0.040
MPC		0.13
ClinPred		0.055	T
GERP RS		-10
Varity_R		0.13
gMVP		0.27
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs35809521; hg19: chr1-17657607;