Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_138619.4(GGA3):c.656A>G(p.Glu219Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0104 in 1,614,100 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 9 hom., cov: 32)

Exomes 𝑓: 0.011 ( 105 hom. )

Consequence

GGA3
NM_138619.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.15

Publications

10 publications found

Variant links:

Genes affected

GGA3 (HGNC:17079): (golgi associated, gamma adaptin ear containing, ARF binding protein 3) This gene encodes a member of the Golgi-localized, gamma adaptin ear-containing, ARF-binding (GGA) family. This family includes ubiquitous coat proteins that regulate the trafficking of proteins between the trans-Golgi network and the lysosome. These proteins share an amino-terminal VHS domain which mediates sorting of the mannose 6-phosphate receptors at the trans-Golgi network. They also contain a carboxy-terminal region with homology to the ear domain of gamma-adaptins. Multiple alternatively spliced transcript variants have been identified in this gene. [provided by RefSeq, Feb 2010]

GGA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009640485).

BP6

Variant 17-75242427-T-C is Benign according to our data. Variant chr17-75242427-T-C is described in ClinVar as Benign. ClinVar VariationId is 2648250.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138619.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GGA3	NM_138619.4	MANE Select	c.656A>G	p.Glu219Gly	missense	Exon 8 of 17	NP_619525.1
GGA3	NM_014001.5		c.557A>G	p.Glu186Gly	missense	Exon 7 of 16	NP_054720.1
GGA3	NM_001172703.3		c.440A>G	p.Glu147Gly	missense	Exon 8 of 17	NP_001166174.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GGA3	ENST00000537686.6	TSL:1 MANE Select	c.656A>G	p.Glu219Gly	missense	Exon 8 of 17	ENSP00000438085.3
GGA3	ENST00000538886.5	TSL:1	c.557A>G	p.Glu186Gly	missense	Exon 7 of 16	ENSP00000446421.2
GGA3	ENST00000621870.4	TSL:1	n.*615A>G		non_coding_transcript_exon	Exon 9 of 18	ENSP00000479464.1

Frequencies

GnomAD3 genomes

AF:

0.00775

AC:

1179

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0157

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00728

AC:

1831

AN:

251488

AF XY:

0.00733

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00367

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0162

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.00814

GnomAD4 exome

AF:

0.0107

AC:

15676

AN:

1461770

Hom.:

105

Cov.:

AF XY:

0.0104

AC XY:

7586

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.00167

AC:

AN:

33478

American (AMR)

AF:

0.00212

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00451

AC:

118

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00278

AC:

240

AN:

86256

European-Finnish (FIN)

AF:

0.0163

AC:

871

AN:

53416

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0123

AC:

13715

AN:

1111900

Other (OTH)

AF:

0.00945

AC:

571

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

792

1585

2377

3170

3962

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

524

1048

1572

2096

2620

<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:

0.00774

AC:

1179

AN:

152330

Hom.:

Cov.:

AF XY:

0.00737

AC XY:

549

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00185

AC:

AN:

41572

American (AMR)

AF:

0.00248

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0157

AC:

167

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0127

AC:

864

AN:

68022

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

127

190

254

317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00991

Hom.:

Bravo

AF:

0.00646

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.0112

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00965

AC:

ExAC

AF:

0.00727

AC:

883

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00867

EpiControl

AF:

0.00990

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0096

MetaSVM

Benign

-0.45

MutationAssessor

Pathogenic

3.0

PhyloP100

6.2

PrimateAI

Uncertain

0.50

REVEL

Uncertain

0.40

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.73

MVP

0.86

ClinPred

0.035

GERP RS

4.8

Varity_R

0.90

gMVP

0.25

Mutation Taster

=35/65

disease causing

(source)

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

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

rs52809447

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over