chr1-75789959-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004582.4(RABGGTB):​c.317C>T​(p.Thr106Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000368 in 1,602,948 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000037 ( 1 hom. )

Consequence

RABGGTB
NM_004582.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.07
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17456949).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RABGGTBNM_004582.4 linkc.317C>T p.Thr106Met missense_variant Exon 4 of 9 ENST00000319942.8 NP_004573.2 P53611Q6IB63A8KAJ2
RABGGTBNR_073562.1 linkn.395C>T non_coding_transcript_exon_variant Exon 4 of 11

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RABGGTBENST00000319942.8 linkc.317C>T p.Thr106Met missense_variant Exon 4 of 9 1 NM_004582.4 ENSP00000317473.3 P53611

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
152056
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000802
AC:
20
AN:
249244
Hom.:
0
AF XY:
0.0000668
AC XY:
9
AN XY:
134706
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000295
Gnomad ASJ exome
AF:
0.000697
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000199
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000531
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000365
AC:
53
AN:
1450774
Hom.:
1
Cov.:
30
AF XY:
0.0000401
AC XY:
29
AN XY:
722362
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000453
Gnomad4 ASJ exome
AF:
0.000307
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000208
Gnomad4 OTH exome
AF:
0.000117
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152174
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000135
Hom.:
0
Bravo
AF:
0.0000491
ExAC
AF:
0.0000906
AC:
11
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 17, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.317C>T (p.T106M) alteration is located in exon 4 (coding exon 4) of the RABGGTB gene. This alteration results from a C to T substitution at nucleotide position 317, causing the threonine (T) at amino acid position 106 to be replaced by a methionine (M). 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
Benign
0.089
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.42
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.056
T;T
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.97
D;D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
L;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-0.84
N;N
REVEL
Benign
0.11
Sift
Benign
0.038
D;T
Sift4G
Benign
0.081
T;T
Polyphen
0.85
P;.
Vest4
0.45
MVP
0.55
MPC
1.5
ClinPred
0.24
T
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.15
gMVP
0.31

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs563619939; hg19: chr1-76255644; API