rs1422626808

Variant names:

• chr1-17372308-C-A
• rs1422626808
• NM_207421.4:c.63C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-17372308-C-A
• chr1-17372308-C-G
• chr1-17372308-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207421.4(PADI6):​c.63C>A​(p.Ser21Arg) 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. 10/13 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PADI6 NM_207421.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.95
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• preimplantation embryonic lethality 2

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06907585).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207421.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI6	NM_207421.4	MANE Select	c.63C>A	p.Ser21Arg	missense	Exon 1 of 16	NP_997304.3	Q6TGC4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI6	ENST00000619609.1	TSL:1 MANE Select	c.63C>A	p.Ser21Arg	missense	Exon 1 of 16	ENSP00000483125.1	Q6TGC4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000193 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	0.0090
DANN	Benign	0.76
DEOGEN2	Benign	0.0067	T
FATHMM_MKL	Benign	0.011	N
MetaRNN	Benign	0.069	T
MutationAssessor	Benign	2.0	M
PhyloP100		-3.0
PrimateAI	Benign	0.25	T
Sift4G	Benign	0.47	T
Vest4		0.18
MVP		0.067
GERP RS		-4.7
PromoterAI		-0.0082	Neutral
Varity_R		0.060
gMVP		0.13

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

Other links and lift over

dbSNP: rs1422626808; hg19: chr1-17698803;