dbSNP rs200053998: PGA5:p.Lys222Gln (chr11-61248426-A-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014224.5(PGA5):c.664A>C(p.Lys222Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 152,138 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 14 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 31 hom. )

Failed GnomAD Quality Control

Consequence

PGA5
NM_014224.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.83

Variant links:

Genes affected

PGA5 (HGNC:8887): (pepsinogen A5) 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]

PGA5 links:

ENSG00000256220 (HGNC:):

ENSG00000256220 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047968924).

BP6

Variant 11-61248426-A-C is Benign according to our data. Variant chr11-61248426-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2641821.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGA5	NM_014224.5 link	c.664A>C	p.Lys222Gln	missense_variant	Exon 6 of 9	ENST00000312403.10	NP_055039.1	P0DJD9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PGA5	ENST00000312403.10 link	c.664A>C	p.Lys222Gln	missense_variant	Exon 6 of 9	1	NM_014224.5	ENSP00000309542.6	P0DJD9
PGA5	ENST00000451616.6 link	c.202A>C	p.Lys68Gln	missense_variant	Exon 1 of 4	2		ENSP00000408739.2	C9JM59
ENSG00000256220	ENST00000537594.1 link	n.160A>C		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.00421

AC:

640

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00591

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00412

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00309

AC:

775

AN:

251000

Hom.:

AF XY:

0.00293

AC XY:

397

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.00432

Gnomad AMR exome

AF:

0.00327

Gnomad ASJ exome

AF:

0.00476

Gnomad EAS exome

AF:

0.00109

Gnomad SAS exome

AF:

0.00222

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00366

Gnomad OTH exome

AF:

0.00652

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00194

AC:

2823

AN:

1456138

Hom.:

Cov.:

AF XY:

0.00194

AC XY:

1409

AN XY:

724632

show subpopulations

Gnomad4 AFR exome

AF:

0.00375

Gnomad4 AMR exome

AF:

0.00311

Gnomad4 ASJ exome

AF:

0.00487

Gnomad4 EAS exome

AF:

0.00108

Gnomad4 SAS exome

AF:

0.000963

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.00190

Gnomad4 OTH exome

AF:

0.00309

GnomAD4 genome

AF:

0.00421

AC:

641

AN:

152138

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

289

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00592

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00412

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00425

Hom.:

Bravo

AF:

0.00472

ExAC

AF:

0.00319

AC:

387

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PGA5: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.0080

DANN

Benign

0.62

DEOGEN2

Benign

0.0050

T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0025

LIST_S2

Benign

0.0050

T;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.0048

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.80

N;.

PrimateAI

Uncertain

0.55

PROVEAN

Benign

1.4

N;N

REVEL

Benign

0.063

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Vest4

0.11

MVP

0.061

MPC

0.51

ClinPred

0.0017

GERP RS

-5.0

Varity_R

0.064

gMVP

0.12

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