NM_002638.4:c.*123C>T

Variant names:

• chr20-45176491-C-T
• rs34412950
• NM_002638.4:c.*123C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002638.4(PI3):​c.*123C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000752 in 252,816 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000089 (0 hom.)
• Consequence: PI3 NM_002638.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 7 publications found

Genes affected

PI3 (HGNC:8947): (peptidase inhibitor 3) This gene encodes an elastase-specific inhibitor that functions as an antimicrobial peptide against Gram-positive and Gram-negative bacteria, and fungal pathogens. The protein contains a WAP-type four-disulfide core (WFDC) domain, and is thus a member of the WFDC domain family. Most WFDC gene members are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the centromeric cluster. Expression of this gene is upgulated by bacterial lipopolysaccharides and cytokines. [provided by RefSeq, Oct 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI3	NM_002638.4	c.*123C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000243924.4	NP_002629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI3	ENST00000243924.4	c.*123C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_002638.4	ENSP00000243924.3

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 152034 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000893 AC: 9 AN: 100782 Hom.: 0 Cov.: 0 AF XY: 0.0000574 AC XY: 3 AN XY: 52236

African (AFR) AF: 0.00 AC: 0 AN: 3566

American (AMR) AF: 0.000202 AC: 1 AN: 4950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3210

East Asian (EAS) AF: 0.00 AC: 0 AN: 5600

South Asian (SAS) AF: 0.000290 AC: 3 AN: 10354

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 468

European-Non Finnish (NFE) AF: 0.0000805 AC: 5 AN: 62114

Other (OTH) AF: 0.00 AC: 0 AN: 6058

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 152034 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74254

African (AFR) AF: 0.0000242 AC: 1 AN: 41394

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.78
PhyloP100		-0.27

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: rs34412950; hg19: chr20-43805132;