NM_032342.3:c.1184G>C

Variant summary

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

The NM_032342.3(PGAP4):​c.1184G>C​(p.Arg395Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R395W) 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

6
9
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.64

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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PGAP4NM_032342.3 linkc.1184G>C p.Arg395Pro 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.1184G>C p.Arg395Pro 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:
1461778
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727192
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33478
American (AMR)
AF:
0.00
AC:
0
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26114
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86242
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111950
Other (OTH)
AF:
0.00
AC:
0
AN:
60388
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
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
Pathogenic
0.95
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T;T;T
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Benign
0.76
.;.;T
M_CAP
Benign
0.042
D
MetaRNN
Uncertain
0.62
D;D;D
MetaSVM
Uncertain
-0.15
T
MutationAssessor
Uncertain
2.3
M;M;M
PhyloP100
7.6
PrimateAI
Uncertain
0.67
T
PROVEAN
Uncertain
-3.1
D;D;D
REVEL
Uncertain
0.42
Sift
Uncertain
0.0040
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.70
MutPred
0.52
Gain of loop (P = 0.024);Gain of loop (P = 0.024);Gain of loop (P = 0.024);
MVP
0.28
MPC
1.0
ClinPred
0.98
D
GERP RS
4.8
Varity_R
0.62
gMVP
0.92
Mutation Taster
=37/63
disease causing

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: rs747987788; hg19: chr9-104238191; API