rs52809447

chr17-75242427-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.15

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 2648250.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GGA3	NM_138619.4	c.656A>G	p.Glu219Gly	missense_variant	8/17	ENST00000537686.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GGA3	ENST00000537686.6	c.656A>G	p.Glu219Gly	missense_variant	8/17	1	NM_138619.4	P1

Frequencies

GnomAD3 genomes AF: 0.00775 AC: 1179 AN: 152212 Hom.: 9 Cov.: 32

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

GnomAD3 exomes AF: 0.00728 AC: 1831 AN: 251488 Hom.: 14 AF XY: 0.00733 AC XY: 996 AN XY: 135916

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 SAS exome AF: 0.00225

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.: 31 AF XY: 0.0104 AC XY: 7586 AN XY: 727210

Gnomad4 AFR exome AF: 0.00167

Gnomad4 AMR exome AF: 0.00212

Gnomad4 ASJ exome AF: 0.00451

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00278

Gnomad4 FIN exome AF: 0.0163

Gnomad4 NFE exome AF: 0.0123

Gnomad4 OTH exome AF: 0.00945

GnomAD4 genome AF: 0.00774 AC: 1179 AN: 152330 Hom.: 9 Cov.: 32 AF XY: 0.00737 AC XY: 549 AN XY: 74490

Gnomad4 AFR AF: 0.00185

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.0157

Gnomad4 NFE AF: 0.0127

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.0107 Hom.: 15

Bravo AF: 0.00646

TwinsUK AF: 0.00971 AC: 36

ALSPAC AF: 0.0112 AC: 43

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.00965 AC: 83

ExAC AF: 0.00727 AC: 883

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00867

EpiControl AF: 0.00990

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

GGA3: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Uncertain	-0.010
Cadd	Pathogenic	29
Dann	Uncertain	0.99
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	T;.;T;T;T;T
MetaRNN	Benign	0.0096	T;T;T;T;T;T
MetaSVM	Benign	-0.45	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.50	T
REVEL	Uncertain	0.40
Sift4G	Uncertain	0.0060	D;D;D;D;D;.
Polyphen		1.0	D;D;.;.;.;.
Vest4		0.73
MVP		0.86
ClinPred		0.035	T
GERP RS		4.8
Varity_R		0.90
gMVP		0.25

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

LitVar

Other links and lift over

dbSNP: rs52809447; hg19: chr17-73238508; COSMIC: COSV105048755; COSMIC: COSV105048755;