rs942459

Variant names:

• chr1-17372842-C-T
• rs942459
• NM_207421.4:c.117-214C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207421.4(PADI6):​c.117-214C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 151,466 control chromosomes in the GnomAD database, including 246 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.050 (246 hom., cov: 32)
• Consequence: PADI6 NM_207421.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI6	NM_207421.4	c.117-214C>T		intron_variant	Intron 1 of 15	ENST00000619609.1	NP_997304.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI6	ENST00000619609.1	c.117-214C>T		intron_variant	Intron 1 of 15	1	NM_207421.4	ENSP00000483125.1

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7495 AN: 151350 Hom.: 246 Cov.: 32

Gnomad AFR AF: 0.0845

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.0312

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0496

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0407

Gnomad OTH AF: 0.0393

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0496 AC: 7514 AN: 151466 Hom.: 246 Cov.: 32 AF XY: 0.0497 AC XY: 3676 AN XY: 74016

African (AFR) AF: 0.0848 AC: 3498 AN: 41272

American (AMR) AF: 0.0229 AC: 349 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3464

East Asian (EAS) AF: 0.0311 AC: 158 AN: 5082

South Asian (SAS) AF: 0.0120 AC: 57 AN: 4760

European-Finnish (FIN) AF: 0.0496 AC: 520 AN: 10480

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0407 AC: 2765 AN: 67878

Other (OTH) AF: 0.0384 AC: 81 AN: 2108

Alfa AF: 0.0387 Hom.: 198

Bravo AF: 0.0479

Asia WGS AF: 0.0270 AC: 98 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.042
DANN	Benign	0.52
PhyloP100		-1.4

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: rs942459; hg19: chr1-17699337;