rs138598204

Variant names:

• chr1-75792299-C-G
• rs138598204
• NM_004582.4:c.698C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-75792299-C-G
• chr1-75792299-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004582.4(RABGGTB):​c.698C>G​(p.Pro233Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,402 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P233L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RABGGTB NM_004582.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.88
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.886

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004582.4. 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
	RABGGTB	NM_004582.4	MANE Select	c.698C>G	p.Pro233Arg	missense	Exon 7 of 9	NP_004573.2
	RABGGTB	NR_073562.1		n.971C>G		non_coding_transcript_exon	Exon 9 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABGGTB	ENST00000319942.8	TSL:1 MANE Select	c.698C>G	p.Pro233Arg	missense	Exon 7 of 9	ENSP00000317473.3	P53611
	RABGGTB	ENST00000935155.1		c.704C>G	p.Pro235Arg	missense	Exon 7 of 9	ENSP00000605214.1
	RABGGTB	ENST00000935145.1		c.695C>G	p.Pro232Arg	missense	Exon 7 of 9	ENSP00000605204.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461402 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726974

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111650

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.087	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Pathogenic	4.1	H
PhyloP100		7.9
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-8.3	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.62		Loss of ubiquitination at K235 (P = 0.1355)
MVP		0.65
MPC		1.9
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.83
gMVP		0.85
Mutation Taster		=22/78	disease causing

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

Other links and lift over

dbSNP: rs138598204; hg19: chr1-76257984;