NM_138619.4:c.656_657delAGinsCC

Variant names:

• chr17-75242426-CT-GG
• NM_138619.4:c.656_657delAGinsCC
• GGA3 p.Glu219Ala

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_138619.4(GGA3):​c.656_657delAGinsCC​(p.Glu219Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. E219G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GGA3 NM_138619.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.15
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGA3	NM_138619.4	MANE Select	c.656_657delAGinsCC	p.Glu219Ala	missense	N/A	NP_619525.1	Q9NZ52-1
	GGA3	NM_014001.5		c.557_558delAGinsCC	p.Glu186Ala	missense	N/A	NP_054720.1	Q9NZ52-2
	GGA3	NM_001172703.3		c.440_441delAGinsCC	p.Glu147Ala	missense	N/A	NP_001166174.1	Q9NZ52-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGA3	ENST00000537686.6	TSL:1 MANE Select	c.656_657delAGinsCC	p.Glu219Ala	missense	N/A	ENSP00000438085.3	Q9NZ52-1
	GGA3	ENST00000538886.5	TSL:1	c.557_558delAGinsCC	p.Glu186Ala	missense	N/A	ENSP00000446421.2	Q9NZ52-2
	GGA3	ENST00000621870.4	TSL:1	n.*615_*616delAGinsCC		non_coding_transcript_exon	Exon 9 of 18	ENSP00000479464.1	G3V1K5

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-73238507;