14-23561600-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003917.5(AP1G2):c.1769G>A(p.Arg590Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

AP1G2
NM_003917.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00

Publications

4 publications found

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 links:

AP1G2-AS1 (HGNC:55442): (AP1G2 antisense RNA 1)

AP1G2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.040255755).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003917.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AP1G2	NM_003917.5	MANE Select	c.1769G>A	p.Arg590Gln	missense	Exon 18 of 22	NP_003908.1	O75843
AP1G2	NM_001282475.2		c.1553G>A	p.Arg518Gln	missense	Exon 16 of 20	NP_001269404.1
AP1G2	NM_001354673.2		c.1382G>A	p.Arg461Gln	missense	Exon 17 of 21	NP_001341602.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AP1G2	ENST00000397120.8	TSL:1 MANE Select	c.1769G>A	p.Arg590Gln	missense	Exon 18 of 22	ENSP00000380309.3	O75843
AP1G2	ENST00000308724.9	TSL:1	c.1769G>A	p.Arg590Gln	missense	Exon 17 of 21	ENSP00000312442.5	O75843
AP1G2	ENST00000460049.6	TSL:1	n.1942G>A		non_coding_transcript_exon	Exon 16 of 20

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000557

AC:

AN:

251386

AF XY:

0.0000810

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.000246

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1112000

Other (OTH)

AF:

0.0000497

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

AF:

0.000151

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.000362

AC:

AN:

41416

American (AMR)

AF:

0.000197

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.037

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.75

M_CAP

Benign

0.0030

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

0.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.46

REVEL

Benign

0.014

Sift

Benign

0.10

Sift4G

Benign

0.34

Polyphen

0.020

Vest4

0.077

MVP

0.14

MPC

0.13

ClinPred

0.035

GERP RS

-0.31

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.027

gMVP

0.11

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over