16-372016-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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. 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

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=0.106749654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGAP6	NM_021259.3	c.2287G>A	p.Asp763Asn	missense_variant	Exon 13 of 13	ENST00000431232.7	NP_067082.2
PGAP6	XM_047434413.1	c.1708G>A	p.Asp570Asn	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.2287G>A	p.Asp763Asn	missense_variant	Exon 13 of 13	1	NM_021259.3	ENSP00000401338.2
PGAP6	ENST00000250930.7	c.1708G>A	p.Asp570Asn	missense_variant	Exon 13 of 13	2		ENSP00000250930.3
PGAP6	ENST00000424078.5	c.688G>A	p.Asp230Asn	missense_variant	Exon 4 of 4	3		ENSP00000397620.1

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

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000144

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.83	L;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.049
Sift	Benign	0.095	T;T
Sift4G	Benign	0.24	T;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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-422016;