NM_021259.3:c.2287G>C

Variant names:

• chr16-372016-C-G
• rs780124401
• NM_021259.3:c.2287G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021259.3(PGAP6):​c.2287G>C​(p.Asp763His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. D763Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PGAP6 NM_021259.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05154696).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021259.3. 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
	PGAP6	NM_021259.3	MANE Select	c.2287G>C	p.Asp763His	missense	Exon 13 of 13	NP_067082.2	Q9HCN3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGAP6	ENST00000431232.7	TSL:1 MANE Select	c.2287G>C	p.Asp763His	missense	Exon 13 of 13	ENSP00000401338.2	Q9HCN3
	PGAP6	ENST00000946607.1		c.2476G>C	p.Asp826His	missense	Exon 13 of 13	ENSP00000616666.1
	PGAP6	ENST00000930879.1		c.2308G>C	p.Asp770His	missense	Exon 13 of 13	ENSP00000600938.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460384 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726472

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111848

Other (OTH) AF: 0.0000166 AC: 1 AN: 60376

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Benign	0.46
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.085	N
PhyloP100		1.5
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.028
Sift	Benign	0.30	T
Sift4G	Benign	0.35	T
Polyphen		0.042	B
Vest4		0.098
MutPred		0.29		Loss of ubiquitination at K761 (P = 0.0877)
MVP		0.10
MPC		0.048
ClinPred		0.078	T
GERP RS		-0.20
Varity_R		0.039
gMVP		0.46

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: rs780124401; hg19: chr16-422016;