17-75239457-A-G

Variant names:

• chr17-75239457-A-G
• rs367837492
• NM_138619.4:c.1698T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_138619.4(GGA3):​c.1698T>C​(p.Ser566Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: GGA3 NM_138619.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.786
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=0.786 with no splicing effect.

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.1698T>C	p.Ser566Ser	synonymous	Exon 14 of 17	NP_619525.1	Q9NZ52-1
	GGA3	NM_014001.5		c.1599T>C	p.Ser533Ser	synonymous	Exon 13 of 16	NP_054720.1	Q9NZ52-2
	GGA3	NM_001172703.3		c.1482T>C	p.Ser494Ser	synonymous	Exon 14 of 17	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.1698T>C	p.Ser566Ser	synonymous	Exon 14 of 17	ENSP00000438085.3	Q9NZ52-1
	GGA3	ENST00000538886.5	TSL:1	c.1599T>C	p.Ser533Ser	synonymous	Exon 13 of 16	ENSP00000446421.2	Q9NZ52-2
	GGA3	ENST00000621870.4	TSL:1	n.*1657T>C		non_coding_transcript_exon	Exon 15 of 18	ENSP00000479464.1	G3V1K5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428736 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 710632

African (AFR) AF: 0.0000322 AC: 1 AN: 31022

American (AMR) AF: 0.00 AC: 0 AN: 32284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24250

East Asian (EAS) AF: 0.00 AC: 0 AN: 39546

South Asian (SAS) AF: 0.00 AC: 0 AN: 81116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103156

Other (OTH) AF: 0.00 AC: 0 AN: 58934

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.0
DANN	Benign	0.64
PhyloP100		0.79
PromoterAI		0.021	Neutral

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

Other links and lift over

dbSNP: rs367837492; hg19: chr17-73235538;