1-17381130-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207421.4(PADI6):ā€‹c.519G>Cā€‹(p.Glu173Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000876 in 1,609,154 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000079 ( 0 hom., cov: 32)
Exomes š‘“: 0.000089 ( 1 hom. )

Consequence

PADI6
NM_207421.4 missense

Scores

10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.05
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.036626756).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PADI6NM_207421.4 linkuse as main transcriptc.519G>C p.Glu173Asp missense_variant 5/16 ENST00000619609.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PADI6ENST00000619609.1 linkuse as main transcriptc.519G>C p.Glu173Asp missense_variant 5/161 NM_207421.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152104
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000623
AC:
15
AN:
240878
Hom.:
0
AF XY:
0.0000613
AC XY:
8
AN XY:
130450
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000298
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000119
Gnomad OTH exome
AF:
0.000170
GnomAD4 exome
AF:
0.0000885
AC:
129
AN:
1456932
Hom.:
1
Cov.:
31
AF XY:
0.0000884
AC XY:
64
AN XY:
724168
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000227
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000354
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000102
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152222
Hom.:
0
Cov.:
32
AF XY:
0.000107
AC XY:
8
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000135
Hom.:
0
Bravo
AF:
0.0000869
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000241
AC:
2
ExAC
AF:
0.0000910
AC:
11
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

Premature ovarian failure Uncertain:1
Uncertain significance, criteria provided, single submitterresearchLupski Lab, Baylor-Hopkins CMG, Baylor College of MedicineApr 22, 2019This variant was identified as homozygous in a female individual with hypergonadotropic hypogonadism. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
0.0090
DANN
Benign
0.49
DEOGEN2
Benign
0.0074
T
FATHMM_MKL
Benign
0.014
N
MetaRNN
Benign
0.037
T
MutationAssessor
Benign
-0.41
N
PrimateAI
Benign
0.29
T
Sift4G
Benign
0.59
T
Vest4
0.040
MVP
0.076
GERP RS
-5.4
Varity_R
0.038
gMVP
0.19

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.

Other links and lift over

dbSNP: rs375717303; hg19: chr1-17707625; API