16-372016-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.46
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
PGAP6NM_021259.3 linkc.2287G>A p.Asp763Asn missense_variant Exon 13 of 13 ENST00000431232.7 NP_067082.2 Q9HCN3
PGAP6XM_047434413.1 linkc.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
PGAP6ENST00000431232.7 linkc.2287G>A p.Asp763Asn missense_variant Exon 13 of 13 1 NM_021259.3 ENSP00000401338.2 Q9HCN3
PGAP6ENST00000250930.7 linkc.1708G>A p.Asp570Asn missense_variant Exon 13 of 13 2 ENSP00000250930.3 K4DI83
PGAP6ENST00000424078.5 linkc.688G>A p.Asp230Asn missense_variant Exon 4 of 4 3 ENSP00000397620.1 H0Y5B2

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
show subpopulations
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; API