NM_001079808.6:c.1057C>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001079808.6(PGA4):​c.1057C>G​(p.Leu353Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 0 hom., cov: 5)
Exomes 𝑓: 0.0038 ( 16 hom. )
Failed GnomAD Quality Control

Consequence

PGA4
NM_001079808.6 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.23
Variant links:
Genes affected
PGA4 (HGNC:8886): (pepsinogen A4) 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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0069322586).
BP6
Variant 11-61231421-C-G is Benign according to our data. Variant chr11-61231421-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2214254.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PGA4NM_001079808.6 linkc.1057C>G p.Leu353Val missense_variant Exon 9 of 9 ENST00000378149.9 NP_001073276.1 P0DJD7A0A1S5UZ02B7Z719

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PGA4ENST00000378149.9 linkc.1057C>G p.Leu353Val missense_variant Exon 9 of 9 1 NM_001079808.6 ENSP00000367391.3 P0DJD7

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
117
AN:
31714
Hom.:
0
Cov.:
5
FAILED QC
Gnomad AFR
AF:
0.00783
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00309
Gnomad ASJ
AF:
0.00121
Gnomad EAS
AF:
0.000455
Gnomad SAS
AF:
0.00240
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00758
Gnomad NFE
AF:
0.00178
Gnomad OTH
AF:
0.0114
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00382
AC:
1288
AN:
337266
Hom.:
16
Cov.:
0
AF XY:
0.00371
AC XY:
657
AN XY:
176980
show subpopulations
Gnomad4 AFR exome
AF:
0.0185
Gnomad4 AMR exome
AF:
0.00475
Gnomad4 ASJ exome
AF:
0.00346
Gnomad4 EAS exome
AF:
0.000506
Gnomad4 SAS exome
AF:
0.00259
Gnomad4 FIN exome
AF:
0.00190
Gnomad4 NFE exome
AF:
0.00368
Gnomad4 OTH exome
AF:
0.00530
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00369
AC:
117
AN:
31750
Hom.:
0
Cov.:
5
AF XY:
0.00393
AC XY:
57
AN XY:
14500
show subpopulations
Gnomad4 AFR
AF:
0.00779
Gnomad4 AMR
AF:
0.00308
Gnomad4 ASJ
AF:
0.00121
Gnomad4 EAS
AF:
0.000457
Gnomad4 SAS
AF:
0.00242
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00178
Gnomad4 OTH
AF:
0.0112
Alfa
AF:
0.000687
Hom.:
2

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Apr 12, 2022
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.0010
DANN
Benign
0.48
DEOGEN2
Benign
0.062
T;.;.
Eigen
Benign
-1.9
Eigen_PC
Benign
-2.0
FATHMM_MKL
Benign
0.033
N
LIST_S2
Benign
0.0057
T;.;.
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.0069
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.30
N;.;.
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
0.12
N;N;N
REVEL
Benign
0.040
Sift
Benign
0.48
T;T;T
Sift4G
Benign
0.59
T;T;T
Vest4
0.042
MutPred
0.14
Gain of sheet (P = 0.1945);.;.;
MVP
0.014
ClinPred
0.0094
T
GERP RS
-3.2
Varity_R
0.090
gMVP
0.063

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: rs1329070174; hg19: chr11-60998893; API