NM_021259.3:c.2032G>T

Variant names:

• chr16-372271-C-A
• rs139793210
• NM_021259.3:c.2032G>T

Variant summary

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

The NM_021259.3(PGAP6):​c.2032G>T​(p.Gly678Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G678R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PGAP6 NM_021259.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.60

Genes affected

PGAP6 (HGNC:17205): (post-GPI attachment to proteins 6) Predicted to enable phospholipase A2 activity. Located in extracellular exosome and lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.25240743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGAP6	NM_021259.3	c.2032G>T	p.Gly678Trp	missense_variant	Exon 13 of 13	ENST00000431232.7	NP_067082.2
PGAP6	XM_047434413.1	c.1453G>T	p.Gly485Trp	missense_variant	Exon 14 of 14		XP_047290369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGAP6	ENST00000431232.7	c.2032G>T	p.Gly678Trp	missense_variant	Exon 13 of 13	1	NM_021259.3	ENSP00000401338.2
PGAP6	ENST00000250930.7	c.1453G>T	p.Gly485Trp	missense_variant	Exon 13 of 13	2		ENSP00000250930.3
PGAP6	ENST00000424078.5	c.433G>T	p.Gly145Trp	missense_variant	Exon 4 of 4	3		ENSP00000397620.1
PGAP6	ENST00000448854.1	c.*271G>T		downstream_gene_variant		2		ENSP00000401931.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0099	T;.
Eigen	Benign	0.093
Eigen_PC	Benign	-0.049
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.18
Sift	Benign	0.18	T;T
Sift4G	Uncertain	0.051	T;T
Polyphen		1.0	D;.
Vest4		0.42
MutPred		0.46		Gain of catalytic residue at G678 (P = 0.0117);.;
MVP		0.29
MPC		0.31
ClinPred		0.85	D
GERP RS		0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.059
gMVP		0.55

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: rs139793210; hg19: chr16-422271; COSMIC: COSV99170652; COSMIC: COSV99170652;