11-61204153-C-T

Variant names:

• chr11-61204153-C-T
• rs1299591409
• NM_001079807.4:c.103C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001079807.4(PGA3):​c.103C>T​(p.Arg35Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 16)
  • Exomes 𝑓: 0.0000032 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PGA3 NM_001079807.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.71
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1646272).

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.103C>T	p.Arg35Cys	missense	Exon 2 of 9	NP_001073275.1	P0DJD8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGA3	ENST00000325558.11	TSL:1 MANE Select	c.103C>T	p.Arg35Cys	missense	Exon 2 of 9	ENSP00000322192.6	P0DJD8
	PGA3	ENST00000535551.1	TSL:3	n.847C>T		non_coding_transcript_exon	Exon 1 of 3
	PGA3	ENST00000537954.5	TSL:2	n.153C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD2 exomes AF: 0.00000551 AC: 1 AN: 181526 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000125

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000316 AC: 4 AN: 1267736 Hom.: 0 Cov.: 26 AF XY: 0.00000157 AC XY: 1 AN XY: 635080

African (AFR) AF: 0.00 AC: 0 AN: 27870

American (AMR) AF: 0.00 AC: 0 AN: 42672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23320

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49464

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3442

European-Non Finnish (NFE) AF: 0.00000317 AC: 3 AN: 946368

Other (OTH) AF: 0.00 AC: 0 AN: 53282

GnomAD4 genome Cov.: 16

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.1
DANN	Benign	0.88
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.098	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.9	L
PhyloP100		-1.7
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.14
MutPred		0.53		Loss of disorder (P = 0.0098)
MVP		0.043
MPC		2.9
ClinPred		0.82	D
GERP RS		-7.3
Varity_R		0.20
gMVP		0.12
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1299591409; hg19: chr11-60971625; COSMIC: COSV100337347; COSMIC: COSV100337347;