14-24267689-C-T

Variant summary

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

The NM_182836.3(RABGGTA):​c.1324G>A​(p.Glu442Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,611,700 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 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

RABGGTA
NM_182836.3 missense

Scores

1
5
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=0.2744575).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RABGGTANM_182836.3 linkc.1324G>A p.Glu442Lys missense_variant Exon 14 of 17 ENST00000216840.11 NP_878256.1 Q92696
RABGGTANM_004581.5 linkc.1324G>A p.Glu442Lys 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.1324G>A p.Glu442Lys missense_variant Exon 14 of 17 1 NM_182836.3 ENSP00000216840.6 Q92696

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000201
AC:
5
AN:
248624
Hom.:
0
AF XY:
0.00000741
AC XY:
1
AN XY:
134890
show subpopulations
Gnomad AFR exome
AF:
0.000129
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000557
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.00000891
AC:
13
AN:
1459522
Hom.:
0
Cov.:
31
AF XY:
0.00000826
AC XY:
6
AN XY:
726050
show subpopulations
Gnomad4 AFR exome
AF:
0.0000599
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000810
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000386
Hom.:
0
Bravo
AF:
0.0000491
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1324G>A (p.E442K) 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 1324, causing the glutamic acid (E) at amino acid position 442 to be replaced by a lysine (K). 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
Uncertain
0.39
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T;T;.
Eigen
Benign
0.0033
Eigen_PC
Benign
0.13
FATHMM_MKL
Pathogenic
0.97
D
M_CAP
Benign
0.0056
T
MetaRNN
Benign
0.27
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.4
M;M;.
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-1.6
N;N;N
REVEL
Benign
0.14
Sift
Uncertain
0.020
D;D;D
Sift4G
Benign
0.29
T;T;T
Polyphen
0.083
B;B;.
Vest4
0.54
MVP
0.56
MPC
0.17
ClinPred
0.50
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.15
gMVP
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs751373180; hg19: chr14-24736895; COSMIC: COSV99253326; COSMIC: COSV99253326; API