1-17278206-G-C

Variant names:

• chr1-17278206-G-C
• rs2977299
• NM_016233.2:c.1555+1330G>C

Variant summary

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

The NM_016233.2(PADI3):​c.1555+1330G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 152,124 control chromosomes in the GnomAD database, including 24,396 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 0.56 (24396 hom., cov: 34)
• Consequence: PADI3 NM_016233.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 6 publications found

Genes affected

PADI3 (HGNC:18337): (peptidyl arginine deiminase 3) 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. The type III enzyme modulates hair structural proteins, such as filaggrin in the hair follicle and trichohyalin in the inner root sheath, during hair follicle formation. Together with the type I enzyme, this enzyme may also play a role in terminal differentiation of the epidermis. This gene exists in a cluster with four other paralogous genes. [provided by RefSeq, Jul 2008]

MIR3972 (HGNC:41876): (microRNA 3972) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016233.2. 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
	PADI3	NM_016233.2	MANE Select	c.1555+1330G>C		intron	N/A	NP_057317.2
	MIR3972	NR_039768.1		n.*231G>C		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI3	ENST00000375460.3	TSL:1 MANE Select	c.1555+1330G>C		intron	N/A	ENSP00000364609.3
	MIR3972	ENST00000582732.1	TSL:6	n.*231G>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.559 AC: 85046 AN: 152006 Hom.: 24341 Cov.: 34

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.560 AC: 85165 AN: 152124 Hom.: 24396 Cov.: 34 AF XY: 0.559 AC XY: 41536 AN XY: 74346

African (AFR) AF: 0.684 AC: 28405 AN: 41514

American (AMR) AF: 0.522 AC: 7975 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1312 AN: 3466

East Asian (EAS) AF: 0.366 AC: 1894 AN: 5180

South Asian (SAS) AF: 0.510 AC: 2463 AN: 4826

European-Finnish (FIN) AF: 0.527 AC: 5572 AN: 10568

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35729 AN: 67976

Other (OTH) AF: 0.538 AC: 1133 AN: 2106

Alfa AF: 0.548 Hom.: 2884

Bravo AF: 0.564

Asia WGS AF: 0.518 AC: 1805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.50
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs2977299; hg19: chr1-17604701;