chr11-61211183-C-T

Variant names:

• chr11-61211183-C-T
• rs769020840
• NM_001079807.4:c.867C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001079807.4(PGA3):​c.867C>T​(p.Pro289Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (0 hom., cov: 7)
  • Exomes 𝑓: 0.0063 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: PGA3 NM_001079807.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.329
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 11-61211183-C-T is Benign according to our data. Variant chr11-61211183-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3777979.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.329 with no splicing effect.

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.867C>T	p.Pro289Pro	synonymous	Exon 7 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.867C>T	p.Pro289Pro	synonymous	Exon 7 of 9	ENSP00000322192.6	P0DJD8
	PGA3	ENST00000543505.5	TSL:3	c.648C>T	p.Pro216Pro	synonymous	Exon 5 of 6	ENSP00000443732.1	F5H842
	PGA3	ENST00000543125.5	TSL:2	c.405C>T	p.Pro135Pro	synonymous	Exon 2 of 4	ENSP00000440177.1	F5GXL4

Frequencies

GnomAD3 genomes AF: 0.00456 AC: 281 AN: 61630 Hom.: 0 Cov.: 7

Gnomad AFR AF: 0.000667

Gnomad AMI AF: 0.0234

Gnomad AMR AF: 0.00744

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.000237

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0185

Gnomad NFE AF: 0.00759

Gnomad OTH AF: 0.0106

GnomAD2 exomes AF: 0.00521 AC: 315 AN: 60404 AF XY: 0.00545

Gnomad AFR exome AF: 0.00107

Gnomad AMR exome AF: 0.00607

Gnomad ASJ exome AF: 0.0104

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00875

Gnomad OTH exome AF: 0.0101

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00626 AC: 2760 AN: 440628 Hom.: 1 Cov.: 4 AF XY: 0.00603 AC XY: 1391 AN XY: 230626

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00130 AC: 17 AN: 13108

American (AMR) AF: 0.00597 AC: 117 AN: 19610

Ashkenazi Jewish (ASJ) AF: 0.0100 AC: 124 AN: 12394

East Asian (EAS) AF: 0.00 AC: 0 AN: 31842

South Asian (SAS) AF: 0.00143 AC: 67 AN: 46848

European-Finnish (FIN) AF: 0.000640 AC: 17 AN: 26558

Middle Eastern (MID) AF: 0.0258 AC: 44 AN: 1706

European-Non Finnish (NFE) AF: 0.00826 AC: 2181 AN: 263890

Other (OTH) AF: 0.00782 AC: 193 AN: 24672

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00456 AC: 281 AN: 61652 Hom.: 0 Cov.: 7 AF XY: 0.00453 AC XY: 128 AN XY: 28278

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000665 AC: 12 AN: 18036

American (AMR) AF: 0.00742 AC: 42 AN: 5662

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 15 AN: 1436

East Asian (EAS) AF: 0.000238 AC: 1 AN: 4202

South Asian (SAS) AF: 0.00 AC: 0 AN: 2190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3680

Middle Eastern (MID) AF: 0.0203 AC: 3 AN: 148

European-Non Finnish (NFE) AF: 0.00760 AC: 191 AN: 25144

Other (OTH) AF: 0.0104 AC: 8 AN: 770

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00142 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		0.33
PromoterAI		0.0046	Neutral
Mutation Taster		=100/0	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: rs769020840; hg19: chr11-60978655;