NM_013365.5:c.764G>T

Variant names:

• chr22-37623565-G-T
• NM_013365.5:c.764G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_013365.5(GGA1):​c.764G>T​(p.Arg255Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GGA1 NM_013365.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.95

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.839

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGA1	NM_013365.5	c.764G>T	p.Arg255Leu	missense_variant	Exon 9 of 17	ENST00000343632.9	NP_037497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGA1	ENST00000343632.9	c.764G>T	p.Arg255Leu	missense_variant	Exon 9 of 17	1	NM_013365.5	ENSP00000341344.4
GGA1	ENST00000381756.9	c.815G>T	p.Arg272Leu	missense_variant	Exon 9 of 17	1		ENSP00000371175.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459602 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725994

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;.;.;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D;D;D
M_CAP	Benign	0.059	D
MetaRNN	Pathogenic	0.84	D;D;D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.7	M;.;M;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.8	D;D;D;D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Uncertain	0.017	D;D;D;D
Polyphen		0.46	P;.;.;.
Vest4		0.91
MutPred		0.65		.;Loss of disorder (P = 0.0351);.;.;
MVP		0.68
MPC		0.96
ClinPred		1.0	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.95
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-38019572;