Genetic Variant PGA3:p.Ser300Ser (chr11-61211216-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001079807.4(PGA3):c.900C>T(p.Ser300Ser) 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 0.00018 ( 0 hom., cov: 11)

Exomes 𝑓: 0.00025 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PGA3
NM_001079807.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.20

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 11-61211216-C-T is Benign according to our data. Variant chr11-61211216-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3770910.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.2 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.900C>T	p.Ser300Ser	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.900C>T	p.Ser300Ser	synonymous	Exon 7 of 9	ENSP00000322192.6	P0DJD8
PGA3	ENST00000543505.5	TSL:3	c.681C>T	p.Ser227Ser	synonymous	Exon 5 of 6	ENSP00000443732.1	F5H842
PGA3	ENST00000543125.5	TSL:2	c.438C>T	p.Ser146Ser	synonymous	Exon 2 of 4	ENSP00000440177.1	F5GXL4

Frequencies

GnomAD3 genomes

AF:

0.000176

AC:

AN:

85084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000405

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000123

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0109

Gnomad NFE

AF:

0.000310

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000229

AC:

AN:

69772

AF XY:

0.000253

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000152

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000566

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000252

AC:

125

AN:

496236

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

AN XY:

257360

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:

14512

American (AMR)

AF:

0.000189

AC:

AN:

21116

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13122

East Asian (EAS)

AF:

0.00

AC:

AN:

32272

South Asian (SAS)

AF:

0.00

AC:

AN:

49554

European-Finnish (FIN)

AF:

0.0000335

AC:

AN:

29862

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1816

European-Non Finnish (NFE)

AF:

0.000368

AC:

113

AN:

307134

Other (OTH)

AF:

0.000261

AC:

AN:

26848

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 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: 0.304

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000176

AC:

AN:

85132

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

40206

show subpopulations

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

African (AFR)

AF:

0.0000404

AC:

AN:

24770

American (AMR)

AF:

0.000122

AC:

AN:

8178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2000

East Asian (EAS)

AF:

0.00

AC:

AN:

4774

South Asian (SAS)

AF:

0.00

AC:

AN:

2824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5392

Middle Eastern (MID)

AF:

0.0116

AC:

AN:

172

European-Non Finnish (NFE)

AF:

0.000310

AC:

AN:

35460

Other (OTH)

AF:

0.00

AC:

AN:

1032

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000667056), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.365

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

9.6

(source)

DANN

Benign

0.50

PhyloP100

-1.2

PromoterAI

-0.051

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over