1-75792302-A-G

Variant names:

• chr1-75792302-A-G
• NM_004582.4:c.701A>G

Variant summary

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

The NM_004582.4(RABGGTB):​c.701A>G​(p.Glu234Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RABGGTB NM_004582.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.29

Genes affected

RABGGTB (HGNC:9796): (Rab geranylgeranyltransferase subunit beta) This gene encodes the beta-subunit of the enzyme Rab geranylgeranyl-transferase (RabGGTase), which belongs to the protein prenyltransferase family. RabGGTase catalyzes the post-translational addition of geranylgeranyl groups to C-terminal cysteine residues of Rab GTPases. Three small nucleolar RNA genes are present in the intronic regions of this gene. Alternately spliced transcript variants have been observed for this gene. A pseudogene associated with this gene is located on chromosome 3. [provided by RefSeq, Jan 2013]

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, 0.785

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABGGTB	NM_004582.4	c.701A>G	p.Glu234Gly	missense_variant	Exon 7 of 9	ENST00000319942.8	NP_004573.2
RABGGTB	NR_073562.1	n.974A>G		non_coding_transcript_exon_variant	Exon 9 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABGGTB	ENST00000319942.8	c.701A>G	p.Glu234Gly	missense_variant	Exon 7 of 9	1	NM_004582.4	ENSP00000317473.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.701A>G (p.E234G) alteration is located in exon 7 (coding exon 7) of the RABGGTB gene. This alteration results from a A to G substitution at nucleotide position 701, causing the glutamic acid (E) at amino acid position 234 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.29	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.58		Loss of sheet (P = 0.0457);
MVP		0.61
MPC		2.0
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.89
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr1-76257987;