9-101476627-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032342.3(PGAP4):​c.466A>G​(p.Lys156Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. K156Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PGAP4
NM_032342.3 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.72

Publications

0 publications found
Variant links:
Genes affected
PGAP4 (HGNC:28180): (post-GPI attachment to proteins GalNAc transferase 4) Enables glycosyltransferase activity. Involved in GPI anchor biosynthetic process. Located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]
TMEM246-AS1 (HGNC:51191): (TMEM246 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.081590146).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PGAP4NM_032342.3 linkc.466A>G p.Lys156Glu missense_variant Exon 2 of 2 ENST00000374848.8 NP_115718.1 Q9BRR3A0A024R188

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PGAP4ENST00000374848.8 linkc.466A>G p.Lys156Glu missense_variant Exon 2 of 2 1 NM_032342.3 ENSP00000363981.3 Q9BRR3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461890
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727246
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53416
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1112012
Other (OTH)
AF:
0.00
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.044
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
21
DANN
Benign
0.93
DEOGEN2
Benign
0.018
T;T;T
Eigen
Benign
-0.18
Eigen_PC
Benign
0.019
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.81
.;.;T
M_CAP
Benign
0.0025
T
MetaRNN
Benign
0.082
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.1
L;L;L
PhyloP100
1.7
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.56
N;N;N
REVEL
Benign
0.069
Sift
Benign
0.65
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.19
B;B;B
Vest4
0.22
MutPred
0.27
Loss of ubiquitination at K156 (P = 0.0174);Loss of ubiquitination at K156 (P = 0.0174);Loss of ubiquitination at K156 (P = 0.0174);
MVP
0.088
MPC
0.61
ClinPred
0.22
T
GERP RS
5.8
Varity_R
0.070
gMVP
0.43
Mutation Taster
=87/13
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

Publications

Other links and lift over

dbSNP: rs1291116519; hg19: chr9-104238909; API