NM_012387.3:c.322C>G

Variant names:

• chr1-17333991-C-G
• rs749986382
• NM_012387.3:c.322C>G

Variant summary

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

The NM_012387.3(PADI4):​c.322C>G​(p.Leu108Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: PADI4 NM_012387.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3	c.322C>G	p.Leu108Val	missense_variant	Exon 3 of 16	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.322C>G	p.Leu108Val	missense_variant	Exon 3 of 16	1	NM_012387.3	ENSP00000364597.4
PADI4	ENST00000375453.5	c.322C>G	p.Leu108Val	missense_variant	Exon 3 of 4	2		ENSP00000364602.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 30

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.322C>G (p.L108V) alteration is located in exon 3 (coding exon 3) of the PADI4 gene. This alteration results from a C to G substitution at nucleotide position 322, causing the leucine (L) at amino acid position 108 to be replaced by a valine (V). 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	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T;T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.82	D
M_CAP	Benign	0.0090	T
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	.;M
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.5	D;N
REVEL	Benign	0.16
Sift	Uncertain	0.0020	D;T
Sift4G	Uncertain	0.017	D;T
Polyphen		0.89	.;P
Vest4		0.53
MutPred		0.77		Gain of phosphorylation at Y109 (P = 0.1172);Gain of phosphorylation at Y109 (P = 0.1172);
MVP		0.18
MPC		0.40
ClinPred		0.95	D
GERP RS		3.8
Varity_R		0.48
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs749986382; hg19: chr1-17660486;