rs780589375

Variant names:

• chr16-2214011-C-G
• rs780589375
• NM_001042371.3:c.683G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-2214011-C-G
• chr16-2214011-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001042371.3(PGP):​c.683G>C​(p.Arg228Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. R228H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PGP NM_001042371.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.68

Genes affected

PGP (HGNC:8909): (phosphoglycolate phosphatase) Enables glycerol-3-phosphatase activity and phosphoglycolate phosphatase activity. Involved in glycerol biosynthetic process; glycerophospholipid metabolic process; and negative regulation of gluconeogenesis. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.875

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGP	NM_001042371.3	c.683G>C	p.Arg228Pro	missense_variant	Exon 2 of 2	ENST00000333503.8	NP_001035830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGP	ENST00000333503.8	c.683G>C	p.Arg228Pro	missense_variant	Exon 2 of 2	1	NM_001042371.3	ENSP00000330918.7
PGP	ENST00000562001.1	n.-113G>C		upstream_gene_variant		2		ENSP00000457909.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Pathogenic	3.6	H
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Uncertain	0.62
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.69		Loss of MoRF binding (P = 0.0975);
MVP		0.27
MPC		1.7
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.94
gMVP		0.99

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: rs780589375; hg19: chr16-2264012;