rs200053998

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

1
18

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]

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
PGA5NM_014224.5 linkc.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 Appris UniProt
PGA5ENST00000312403.10 linkc.664A>C p.Lys222Gln missense_variant Exon 6 of 9 1 NM_014224.5 ENSP00000309542.6 P0DJD9
PGA5ENST00000451616.6 linkc.202A>C p.Lys68Gln missense_variant Exon 1 of 4 2 ENSP00000408739.2 C9JM59
ENSG00000256220ENST00000537594.1 linkn.160A>C non_coding_transcript_exon_variant Exon 2 of 2 5

Frequencies

GnomAD3 genomes
AF:
0.00421
AC:
640
AN:
152020
Hom.:
14
Cov.:
32
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.:
10
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.:
31
Cov.:
31
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.:
14
Cov.:
32
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.:
0
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
T
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
N
LIST_S2
Benign
0.0050
T;T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.0048
T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
-0.80
N;.
PrimateAI
Uncertain
0.55
T
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
T
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.

Other links and lift over

dbSNP: rs200053998; hg19: chr11-61015898; COSMIC: COSV56715955; COSMIC: COSV56715955; API