dbSNP rs769020840: PGA3:p.Pro289Pro (chr11-61211183-C-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_001079807.4(PGA3):c.867C>G(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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P289P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 7)

Exomes 𝑓: 0.000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PGA3
NM_001079807.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.329

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP7

Synonymous conserved (PhyloP=0.329 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079807.4. 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
	PGA3	NM_001079807.4	MANE Select	c.867C>G	p.Pro289Pro	synonymous	Exon 7 of 9	NP_001073275.1	P0DJD8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PGA3	ENST00000325558.11	TSL:1 MANE Select	c.867C>G	p.Pro289Pro	synonymous	Exon 7 of 9	ENSP00000322192.6	P0DJD8
PGA3	ENST00000543505.5	TSL:3	c.648C>G	p.Pro216Pro	synonymous	Exon 5 of 6	ENSP00000443732.1	F5H842
PGA3	ENST00000543125.5	TSL:2	c.405C>G	p.Pro135Pro	synonymous	Exon 2 of 4	ENSP00000440177.1	F5GXL4

Frequencies

GnomAD3 genomes

AF:

0.0000162

AC:

AN:

61826

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000396

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000135

AC:

AN:

442992

Hom.:

Cov.:

AF XY:

0.00000431

AC XY:

AN XY:

231834

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

13130

American (AMR)

AF:

0.00

AC:

AN:

19778

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12500

East Asian (EAS)

AF:

0.00

AC:

AN:

31842

South Asian (SAS)

AF:

0.00

AC:

AN:

46960

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1722

European-Non Finnish (NFE)

AF:

0.0000226

AC:

AN:

265612

Other (OTH)

AF:

0.00

AC:

AN:

24868

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000630232), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000162

AC:

AN:

61826

Hom.:

Cov.:

AF XY:

0.0000353

AC XY:

AN XY:

28336

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

18010

American (AMR)

AF:

0.00

AC:

AN:

5674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1444

East Asian (EAS)

AF:

0.00

AC:

AN:

4216

South Asian (SAS)

AF:

0.00

AC:

AN:

2208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3684

Middle Eastern (MID)

AF:

0.00

AC:

AN:

162

European-Non Finnish (NFE)

AF:

0.0000396

AC:

AN:

25284

Other (OTH)

AF:

0.00

AC:

AN:

756

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.61

PhyloP100

0.33

PromoterAI

0.029

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over