GeneBe

rs367610818

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003917.5(AP1G2):ā€‹c.1723G>Cā€‹(p.Asp575His) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. D575N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

AP1G2
NM_003917.5 missense

Scores

3
9
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.86
Variant links:
Genes affected
AP1G2 (HGNC:556): (adaptor related protein complex 1 subunit gamma 2) Adaptins are important components of clathrin-coated vesicles transporting ligand-receptor complexes from the plasma membrane or from the trans-Golgi network to lysosomes. The adaptin family of proteins is composed of four classes of molecules named alpha, beta-, beta prime- and gamma- adaptins. Adaptins, together with medium and small subunits, form a heterotetrameric complex called an adaptor, whose role is to promote the formation of clathrin-coated pits and vesicles. The protein encoded by this gene is a gamma-adaptin protein and it belongs to the adaptor complexes large subunits family. This protein along with the complex is thought to function at some trafficking step in the complex pathways between the trans-Golgi network and the cell surface. [provided by RefSeq, Aug 2017]
AP1G2-AS1 (HGNC:55442): (AP1G2 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.804

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AP1G2NM_003917.5 linkc.1723G>C p.Asp575His missense_variant Exon 17 of 22 ENST00000397120.8 NP_003908.1 O75843

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AP1G2ENST00000397120.8 linkc.1723G>C p.Asp575His missense_variant Exon 17 of 22 1 NM_003917.5 ENSP00000380309.3 O75843

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458092
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
725010
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Uncertain
0.026
T
BayesDel_noAF
Benign
-0.20
CADD
Benign
22
DANN
Benign
0.97
DEOGEN2
Benign
0.29
T;T
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.22
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Pathogenic
0.98
.;D
M_CAP
Benign
0.026
D
MetaRNN
Pathogenic
0.80
D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.8
M;M
PrimateAI
Uncertain
0.62
T
PROVEAN
Pathogenic
-5.1
D;D
REVEL
Benign
0.24
Sift
Uncertain
0.017
D;D
Sift4G
Uncertain
0.035
D;D
Polyphen
0.99
D;D
Vest4
0.81
MutPred
0.40
Gain of MoRF binding (P = 0.0526);Gain of MoRF binding (P = 0.0526);
MVP
0.19
MPC
0.59
ClinPred
0.99
D
GERP RS
4.1
Varity_R
0.52
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr14-24031181; API