11-61230248-G-T

Variant names:

• chr11-61230248-G-T
• rs1854001433
• NM_001079808.6:c.1001G>T

Variant summary

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

The NM_001079808.6(PGA4):​c.1001G>T​(p.Ser334Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S334N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 5)
• Consequence: PGA4 NM_001079808.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440
• Publications: 0 publications found

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]

ENSG00000256220 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.23055735).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079808.6. 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
	PGA4	NM_001079808.6	MANE Select	c.1001G>T	p.Ser334Ile	missense	Exon 8 of 9	NP_001073276.1	A0A1S5UZ02

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGA4	ENST00000378149.9	TSL:1 MANE Select	c.1001G>T	p.Ser334Ile	missense	Exon 8 of 9	ENSP00000367391.3	P0DJD7
	PGA4	ENST00000537932.5	TSL:2	c.539G>T	p.Ser180Ile	missense	Exon 3 of 4	ENSP00000442757.1	F5GXL4
	PGA4	ENST00000544899.1	TSL:2	c.221G>T	p.Ser74Ile	missense	Exon 2 of 3	ENSP00000443623.1	F5H0H6

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 5

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.087	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		0.044
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.13
Sift	Benign	0.030	D
Sift4G	Uncertain	0.021	D
Vest4		0.31
MutPred		0.57		Loss of glycosylation at S334 (P = 0.0251)
MVP		0.16
ClinPred		0.89	D
GERP RS		1.3
Varity_R		0.33
gMVP		0.34
Mutation Taster		=83/17	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: rs1854001433; hg19: chr11-60997720;