16-372016-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021259.3(PGAP6):​c.2287G>A​(p.Asp763Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,460,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 0.000012 (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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.106749654).

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>A	p.Asp763Asn	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>A	p.Asp763Asn	missense	Exon 13 of 13	ENSP00000401338.2	Q9HCN3
	PGAP6	ENST00000946607.1		c.2476G>A	p.Asp826Asn	missense	Exon 13 of 13	ENSP00000616666.1
	PGAP6	ENST00000930879.1		c.2308G>A	p.Asp770Asn	missense	Exon 13 of 13	ENSP00000600938.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1460384 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 726472

African (AFR) AF: 0.0000299 AC: 1 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: 0.0000144 AC: 16 AN: 1111848

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.83	L
PhyloP100		1.5
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.049
Sift	Benign	0.095	T
Sift4G	Benign	0.24	T
Polyphen		0.93	P
Vest4		0.086
MutPred		0.28		Loss of catalytic residue at D763 (P = 0.1106)
MVP		0.11
MPC		0.042
ClinPred		0.15	T
GERP RS		-0.20
Varity_R		0.025
gMVP		0.27
Mutation Taster		=98/2	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: rs780124401; hg19: chr16-422016;