chr10-102259011-CGA-GGC

Variant names:

• chr10-102259011-CGA-GGC
• NM_001377137.1:c.73_75delCGAinsGGC
• GBF1 p.Arg25Gly

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001377137.1(GBF1):​c.73_75delCGAinsGGC​(p.Arg25Gly) variant causes a missense change involving the alteration of a conserved nucleotide. 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. R25Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GBF1 NM_001377137.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.93
• Publications: 0 publications found

Genes affected

GBF1 (HGNC:4181): (golgi brefeldin A resistant guanine nucleotide exchange factor 1) This gene encodes a member of the Sec7 domain family. The encoded protein is a guanine nucleotide exchange factor that regulates the recruitment of proteins to membranes by mediating GDP to GTP exchange. The encoded protein is localized to the Golgi apparatus and plays a role in vesicular trafficking by activating ADP ribosylation factor 1. The encoded protein has also been identified as an important host factor for viral replication. Multiple transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]

GBF1 Gene-Disease associations (from GenCC):

• axonal neuropathy

  Inheritance: AD Classification: STRONG Submitted by: Franklin by Genoox

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377137.1. 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
	GBF1	NM_001377137.1	MANE Select	c.73_75delCGAinsGGC	p.Arg25Gly	missense	N/A	NP_001364066.1	Q92538-4
	GBF1	NM_001411027.1		c.73_75delCGAinsGGC	p.Arg25Gly	missense	N/A	NP_001397956.1	A0A669KBG8
	GBF1	NM_001391922.1		c.73_75delCGAinsGGC	p.Arg25Gly	missense	N/A	NP_001378851.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBF1	ENST00000369983.5	TSL:1 MANE Select	c.73_75delCGAinsGGC	p.Arg25Gly	missense	N/A	ENSP00000359000.4	Q92538-4
	GBF1	ENST00000673650.1		c.73_75delCGAinsGGC	p.Arg25Gly	missense	N/A	ENSP00000501233.1	A0A669KBG8
	GBF1	ENST00000674034.1		c.73_75delCGAinsGGC	p.Arg25Gly	missense	N/A	ENSP00000501064.1	A0A669KB10

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		8.9

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: chr10-104018768;