Genetic Variant NM_001079807.4:c.867C>T (chr11-61211183-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001079807.4(PGA3):c.867C>T(p.Pro289Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 0 hom., cov: 7)

Exomes 𝑓: 0.0063 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

PGA3
NM_001079807.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.329

Variant links:

Genes affected

PGA3 (HGNC:8885): (pepsinogen A3) This gene encodes a protein precursor of the digestive enzyme pepsin, a member of the peptidase A1 family of endopeptidases. The encoded precursor is secreted by gastric chief cells and undergoes autocatalytic cleavage in acidic conditions to form the active enzyme, which functions in the digestion of dietary proteins. This gene is found in a cluster of related genes on chromosome 11, each of which encodes one of multiple pepsinogens. Pepsinogen levels in serum may serve as a biomarker for atrophic gastritis and gastric cancer. [provided by RefSeq, Jul 2015]

PGA3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 11-61211183-C-T is Benign according to our data. Variant chr11-61211183-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3777979.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.329 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGA3	NM_001079807.4 link	c.867C>T	p.Pro289Pro	synonymous_variant	Exon 7 of 9	ENST00000325558.11	NP_001073275.1	P0DJD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGA3	ENST00000325558.11 link	c.867C>T	p.Pro289Pro	synonymous_variant	Exon 7 of 9	1	NM_001079807.4	ENSP00000322192.6		P0DJD8

Frequencies

GnomAD3 genomes

AF:

0.00456

AC:

281

AN:

61630

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000667

Gnomad AMI

AF:

0.0234

Gnomad AMR

AF:

0.00744

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.000237

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0185

Gnomad NFE

AF:

0.00759

Gnomad OTH

AF:

0.0106

GnomAD3 exomes

AF:

0.00521

AC:

315

AN:

60404

Hom.:

AF XY:

0.00545

AC XY:

167

AN XY:

30656

show subpopulations

Gnomad AFR exome

AF:

0.00107

Gnomad AMR exome

AF:

0.00607

Gnomad ASJ exome

AF:

0.0104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00149

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00875

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00626

AC:

2760

AN:

440628

Hom.:

Cov.:

AF XY:

0.00603

AC XY:

1391

AN XY:

230626

show subpopulations

Gnomad4 AFR exome

AF:

0.00130

Gnomad4 AMR exome

AF:

0.00597

Gnomad4 ASJ exome

AF:

0.0100

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00143

Gnomad4 FIN exome

AF:

0.000640

Gnomad4 NFE exome

AF:

0.00826

Gnomad4 OTH exome

AF:

0.00782

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00456

AC:

281

AN:

61652

Hom.:

Cov.:

AF XY:

0.00453

AC XY:

128

AN XY:

28278

show subpopulations

Gnomad4 AFR

AF:

0.000665

Gnomad4 AMR

AF:

0.00742

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.000238

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00760

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00142

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PGA3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over