4-98343189-G-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001100427.2(RAP1GDS1):c.163G>T(p.Ala55Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000756 in 1,455,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000076 ( 0 hom. )
Consequence
RAP1GDS1
NM_001100427.2 missense
NM_001100427.2 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 4.45
Genes affected
RAP1GDS1 (HGNC:9859): (Rap1 GTPase-GDP dissociation stimulator 1) The smg GDP dissociation stimulator (smgGDS) protein is a stimulatory GDP/GTP exchange protein with GTPase activity (Riess et al., 1993 [PubMed 8262526]).[supplied by OMIM, Feb 2010]
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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=0.18924716).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RAP1GDS1 | NM_001100427.2 | c.163G>T | p.Ala55Ser | missense_variant | 3/15 | ENST00000408927.8 | NP_001093897.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAP1GDS1 | ENST00000408927.8 | c.163G>T | p.Ala55Ser | missense_variant | 3/15 | 2 | NM_001100427.2 | ENSP00000386153 | A1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249066Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135150
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GnomAD4 exome AF: 0.00000756 AC: 11AN: 1455216Hom.: 0 Cov.: 30 AF XY: 0.00000966 AC XY: 7AN XY: 724420
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GnomAD4 genome Cov.: 33
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33
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2023 | The c.166G>T (p.A56S) alteration is located in exon 3 (coding exon 3) of the RAP1GDS1 gene. This alteration results from a G to T substitution at nucleotide position 166, causing the alanine (A) at amino acid position 56 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;.;T;.;.;T;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;L;.;.;.;L;.
MutationTaster
Benign
D;D;D;D;D;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;D;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T
Polyphen
0.30, 0.0010
.;.;B;.;.;.;B;.
Vest4
MutPred
0.47
.;.;Gain of disorder (P = 0.0477);Gain of disorder (P = 0.0477);.;.;Gain of disorder (P = 0.0477);.;
MVP
MPC
0.16
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
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Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at