16-2214638-G-A

Variant names:

• chr16-2214638-G-A
• rs1327860197
• NM_001042371.3:c.140C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001042371.3(PGP):​c.140C>T​(p.Pro47Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000108 in 1,295,082 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P47R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: PGP NM_001042371.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.71
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042371.3. 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
	PGP	NM_001042371.3	MANE Select	c.140C>T	p.Pro47Leu	missense	Exon 1 of 2	NP_001035830.1	A6NDG6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGP	ENST00000333503.8	TSL:1 MANE Select	c.140C>T	p.Pro47Leu	missense	Exon 1 of 2	ENSP00000330918.7	A6NDG6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000132 AC: 1 AN: 75504 AF XY: 0.0000227

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000723

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000108 AC: 14 AN: 1295082 Hom.: 0 Cov.: 36 AF XY: 0.0000109 AC XY: 7 AN XY: 639300

African (AFR) AF: 0.00 AC: 0 AN: 26064

American (AMR) AF: 0.00 AC: 0 AN: 24464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22212

East Asian (EAS) AF: 0.00 AC: 0 AN: 27592

South Asian (SAS) AF: 0.00 AC: 0 AN: 70918

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3906

European-Non Finnish (NFE) AF: 0.0000135 AC: 14 AN: 1034500

Other (OTH) AF: 0.00 AC: 0 AN: 53124

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.84	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		4.7
PrimateAI	Pathogenic	0.95	D
PROVEAN	Pathogenic	-6.2	D
REVEL	Benign	0.27
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.075	T
Polyphen		0.99	D
Vest4		0.31
MutPred		0.62		Loss of helix (P = 0.0167)
MVP		0.34
MPC		2.2
ClinPred		0.99	D
GERP RS		3.6
PromoterAI		0.023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.33
gMVP		0.50
Mutation Taster		=56/44	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: rs1327860197; hg19: chr16-2264639;