NM_207421.4:c.286G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1

The NM_207421.4(PADI6):c.286G>A(p.Ala96Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00097 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

PADI6
NM_207421.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.739

Variant links:

Genes affected

PADI6 (HGNC:20449): (peptidyl arginine deiminase 6) This gene encodes a member of the peptidyl arginine deiminase family of enzymes, which catalyze the post-translational deimination of proteins by converting arginine residues into citrullines in the presence of calcium ions. The family members have distinct substrate specificities and tissue-specific expression patterns. This protein may play a role in cytoskeletal reorganization in the egg and in early embryo development. [provided by RefSeq, Sep 2012]

PADI6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.006461054).

BP6

Variant 1-17373225-G-A is Benign according to our data. Variant chr1-17373225-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1176184.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000972 (148/152330) while in subpopulation NFE AF= 0.00179 (122/68032). AF 95% confidence interval is 0.00153. There are 0 homozygotes in gnomad4. There are 66 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI6	NM_207421.4 link	c.286G>A	p.Ala96Thr	missense_variant	Exon 2 of 16	ENST00000619609.1	NP_997304.3	Q6TGC4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI6	ENST00000619609.1 link	c.286G>A	p.Ala96Thr	missense_variant	Exon 2 of 16	1	NM_207421.4	ENSP00000483125.1		Q6TGC4

Frequencies

GnomAD3 genomes

AF:

0.000972

AC:

148

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00179

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00102

AC:

254

AN:

248900

Hom.:

AF XY:

0.00115

AC XY:

155

AN XY:

135024

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.000883

Gnomad NFE exome

AF:

0.00174

Gnomad OTH exome

AF:

0.00265

GnomAD4 exome

AF:

0.00105

AC:

1538

AN:

1461616

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

779

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.00121

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.000972

AC:

148

AN:

152330

Hom.:

Cov.:

AF XY:

0.000886

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.00179

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.000744

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00117

AC:

ExAC

AF:

0.00123

AC:

149

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Aug 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PADI6: BP4 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

PADI6-related disorder

Benign:1

Jan 10, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.0079

FATHMM_MKL

Benign

0.087

MetaRNN

Benign

0.0065

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.22

Sift4G

Uncertain

0.023

Vest4

0.058

MVP

0.13

GERP RS

1.3

Varity_R

0.022

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over