rs1057517681

Positions:

• chr1-17394041-C-G
• chr1-17394041-C-T

Variant summary

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

The NM_207421.4(PADI6):​c.1141C>G​(p.Gln381Glu) 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. 9/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PADI6 NM_207421.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220

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]

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=0.11458188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI6	NM_207421.4	c.1141C>G	p.Gln381Glu	missense_variant	10/16	ENST00000619609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI6	ENST00000619609.1	c.1141C>G	p.Gln381Glu	missense_variant	10/16	1	NM_207421.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.48
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Benign	0.20	N
MetaRNN	Benign	0.11	T
PrimateAI	Benign	0.20	T
Sift4G	Uncertain	0.019	D
Vest4		0.18
MVP		0.24
GERP RS		1.5
Varity_R		0.066
gMVP		0.70

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: rs1057517681; hg19: chr1-17720537;