1-17331039-G-T

Position:

• chr1-17331039-G-T

Variant summary

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

The NM_012387.3(PADI4):​c.163G>T​(p.Gly55Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. G55S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PADI4 NM_012387.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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=0.07256138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI4	NM_012387.3	c.163G>T	p.Gly55Cys	missense_variant	2/16	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.163G>T	p.Gly55Cys	missense_variant	2/16	1	NM_012387.3	ENSP00000364597.4
PADI4	ENST00000375453.5	c.163G>T	p.Gly55Cys	missense_variant	2/4	2		ENSP00000364602.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.0080
DANN	Benign	0.70
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.011	N
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.073	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	.;N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.028
Sift	Benign	0.060	T;D
Sift4G	Benign	0.15	T;T
Polyphen		0.0010	.;B
Vest4		0.11
MutPred		0.34		Loss of disorder (P = 0.0485);Loss of disorder (P = 0.0485);
MVP		0.21
MPC		0.12
ClinPred		0.077	T
GERP RS		-11
Varity_R		0.10
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs11203366; hg19: chr1-17657534;