Genetic Variant GGA1:p.Ile14Val (chr22-37608900-A-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_013365.5(GGA1):c.40A>G(p.Ile14Val) variant causes a missense change. The variant allele was found at a frequency of 0.000115 in 1,314,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

GGA1
NM_013365.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88

Publications

1 publications found

Variant links:

Genes affected

GGA1 (HGNC:17842): (golgi associated, gamma adaptin ear containing, ARF binding protein 1) This gene encodes a member of the Golgi-localized, gamma adaptin ear-containing, ARF-binding (GGA) protein family. Members of this family are 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 encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GGA1 links:

ENSG00000298665 (HGNC:):

ENSG00000298665 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.28667957).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013365.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GGA1	NM_013365.5	MANE Select	c.40A>G	p.Ile14Val	missense	Exon 1 of 17	NP_037497.1	Q9UJY5-1
GGA1	NM_001363771.2		c.40A>G	p.Ile14Val	missense	Exon 1 of 17	NP_001350700.1	Q9UJY5-6
GGA1	NM_001172687.2		c.40A>G	p.Ile14Val	missense	Exon 1 of 17	NP_001166158.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GGA1	ENST00000343632.9	TSL:1 MANE Select	c.40A>G	p.Ile14Val	missense	Exon 1 of 17	ENSP00000341344.4	Q9UJY5-1
GGA1	ENST00000381756.9	TSL:1	c.40A>G	p.Ile14Val	missense	Exon 1 of 17	ENSP00000371175.5	Q9UJY5-6
GGA1	ENST00000325180.12	TSL:1	c.40A>G	p.Ile14Val	missense	Exon 1 of 15	ENSP00000321288.8	Q9UJY5-4

Frequencies

GnomAD3 genomes

AF:

0.0000396

AC:

AN:

151426

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000738

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

6834

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000125

AC:

145

AN:

1162864

Hom.:

Cov.:

AF XY:

0.000126

AC XY:

AN XY:

557174

show subpopulations

African (AFR)

AF:

0.0000430

AC:

AN:

23274

American (AMR)

AF:

0.00

AC:

AN:

8606

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15868

East Asian (EAS)

AF:

0.00

AC:

AN:

26644

South Asian (SAS)

AF:

0.00

AC:

AN:

41690

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3294

European-Non Finnish (NFE)

AF:

0.000149

AC:

144

AN:

963738

Other (OTH)

AF:

0.00

AC:

AN:

47358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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:

0.0000396

AC:

AN:

151426

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

73972

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41174

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5088

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10536

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000738

AC:

AN:

67796

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.00

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000534

AC:

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

0.31

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

0.021

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.73

M_CAP

Benign

0.073

MetaRNN

Benign

0.29

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

3.9

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.72

REVEL

Benign

0.13

Sift

Benign

0.060

Sift4G

Uncertain

0.029

Polyphen

0.016

Vest4

0.35

MutPred

0.67

Gain of methylation at R13 (P = 0.1073)

MVP

0.35

MPC

0.22

ClinPred

0.83

GERP RS

4.8

PromoterAI

0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.46

gMVP

0.21

Mutation Taster

=60/40

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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