14-24267736-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_182836.3(RABGGTA):​c.1277G>A​(p.Arg426His) variant causes a missense change. The variant allele was found at a frequency of 0.00023 in 1,612,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

RABGGTA
NM_182836.3 missense

Scores

4
2
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.28
Variant links:
Genes affected
RABGGTA (HGNC:9795): (Rab geranylgeranyltransferase subunit alpha) Predicted to enable small GTPase binding activity. Predicted to contribute to Rab geranylgeranyltransferase activity. Predicted to be involved in protein geranylgeranylation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35598958).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RABGGTANM_182836.3 linkc.1277G>A p.Arg426His missense_variant Exon 14 of 17 ENST00000216840.11 NP_878256.1 Q92696
RABGGTANM_004581.5 linkc.1277G>A p.Arg426His missense_variant Exon 13 of 16 NP_004572.3 Q92696

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RABGGTAENST00000216840.11 linkc.1277G>A p.Arg426His missense_variant Exon 14 of 17 1 NM_182836.3 ENSP00000216840.6 Q92696

Frequencies

GnomAD3 genomes
AF:
0.000204
AC:
31
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.000382
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000120
AC:
30
AN:
249060
Hom.:
0
AF XY:
0.000133
AC XY:
18
AN XY:
135104
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000230
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000232
AC:
339
AN:
1459858
Hom.:
0
Cov.:
31
AF XY:
0.000204
AC XY:
148
AN XY:
726236
show subpopulations
Gnomad4 AFR exome
AF:
0.0000898
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000277
Gnomad4 OTH exome
AF:
0.000365
GnomAD4 genome
AF:
0.000204
AC:
31
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000382
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000180
Hom.:
0
Bravo
AF:
0.000178
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000117
AC:
1
ExAC
AF:
0.0000742
AC:
9
EpiCase
AF:
0.000218
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
Feb 13, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1277G>A (p.R426H) alteration is located in exon 13 (coding exon 13) of the RABGGTA gene. This alteration results from a G to A substitution at nucleotide position 1277, causing the arginine (R) at amino acid position 426 to be replaced by a histidine (H). 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
0.14
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.31
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.27
T;T;.
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Pathogenic
0.97
D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.36
T;T;T
MetaSVM
Benign
-0.81
T
MutationAssessor
Uncertain
2.2
M;M;.
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-2.7
D;D;N
REVEL
Benign
0.22
Sift
Benign
0.043
D;D;T
Sift4G
Benign
0.39
T;T;T
Polyphen
1.0
D;D;.
Vest4
0.52
MVP
0.64
MPC
0.60
ClinPred
0.66
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.27
gMVP
0.40

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: rs367842090; hg19: chr14-24736942; API