rs372664007

Variant names:

• chr6-41742372-C-G
• rs372664007
• NM_002630.4:c.565G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-41742372-C-G
• chr6-41742372-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002630.4(PGC):​c.565G>C​(p.Val189Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PGC NM_002630.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505

Genes affected

PGC (HGNC:8890): (progastricsin) This gene encodes an aspartic proteinase that belongs to the peptidase family A1. The encoded protein is a digestive enzyme that is produced in the stomach and constitutes a major component of the gastric mucosa. This protein is also secreted into the serum. This protein is synthesized as an inactive zymogen that includes a highly basic prosegment. This enzyme is converted into its active mature form at low pH by sequential cleavage of the prosegment that is carried out by the enzyme itself. Polymorphisms in this gene are associated with susceptibility to gastric cancers. Serum levels of this enzyme are used as a biomarker for certain gastric diseases including Helicobacter pylori related gastritis. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 1. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15251774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGC	NM_002630.4	c.565G>C	p.Val189Leu	missense_variant	Exon 5 of 9	ENST00000373025.7	NP_002621.1
PGC	NM_001166424.2	c.565G>C	p.Val189Leu	missense_variant	Exon 5 of 7		NP_001159896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGC	ENST00000373025.7	c.565G>C	p.Val189Leu	missense_variant	Exon 5 of 9	1	NM_002630.4	ENSP00000362116.3
PGC	ENST00000425343.6	c.565G>C	p.Val189Leu	missense_variant	Exon 5 of 7	2		ENSP00000405094.2
PGC	ENST00000356667.8	c.328G>C	p.Val110Leu	missense_variant	Exon 3 of 4	5		ENSP00000349094.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251404 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135880

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 SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461870 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.75
DANN	Benign	0.69
DEOGEN2	Benign	0.022	T;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.33	T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.6	M;.;M
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.39	T;T;T
Sift4G	Benign	0.32	T;.;T
Polyphen		0.0010	B;.;.
Vest4		0.23
MutPred		0.56		Loss of catalytic residue at V189 (P = 0.0248);.;Loss of catalytic residue at V189 (P = 0.0248);
MVP		0.19
MPC		0.10
ClinPred		0.053	T
GERP RS		-8.8
Varity_R		0.073
gMVP		0.27

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

Other links and lift over

dbSNP: rs372664007; hg19: chr6-41710110;