chr1-17330974-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_012387.3(PADI4):​c.98C>A​(p.Ala33Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000706 in 1,417,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

PADI4
NM_012387.3 missense

Scores

6
8
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.12
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.843

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PADI4NM_012387.3 linkc.98C>A p.Ala33Asp missense_variant Exon 2 of 16 ENST00000375448.4 NP_036519.2 Q9UM07

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PADI4ENST00000375448.4 linkc.98C>A p.Ala33Asp missense_variant Exon 2 of 16 1 NM_012387.3 ENSP00000364597.4 Q9UM07
PADI4ENST00000375453.5 linkc.98C>A p.Ala33Asp missense_variant Exon 2 of 4 2 ENSP00000364602.1 B1AQ67

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.06e-7
AC:
1
AN:
1417156
Hom.:
0
Cov.:
29
AF XY:
0.00000142
AC XY:
1
AN XY:
704098
show subpopulations
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:
9.14e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 20, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.98C>A (p.A33D) alteration is located in exon 2 (coding exon 2) of the PADI4 gene. This alteration results from a C to A substitution at nucleotide position 98, causing the alanine (A) at amino acid position 33 to be replaced by an aspartic acid (D). 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
Pathogenic
0.64
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T;T
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.96
D
M_CAP
Benign
0.044
D
MetaRNN
Pathogenic
0.84
D;D
MetaSVM
Benign
-0.91
T
MutationAssessor
Pathogenic
3.1
.;M
PrimateAI
Uncertain
0.48
T
PROVEAN
Pathogenic
-4.9
D;D
REVEL
Uncertain
0.34
Sift
Uncertain
0.0040
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
.;D
Vest4
0.76
MutPred
0.76
Gain of disorder (P = 0.0442);Gain of disorder (P = 0.0442);
MVP
0.42
MPC
0.65
ClinPred
1.0
D
GERP RS
5.3
Varity_R
0.96
gMVP
0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-17657469; API