rs758022116
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_020336.4(RALGAPB):c.2324G>A(p.Arg775His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
RALGAPB
NM_020336.4 missense
NM_020336.4 missense
Scores
7
4
8
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.63
Genes affected
RALGAPB (HGNC:29221): (Ral GTPase activating protein non-catalytic subunit beta) Enables protein heterodimerization activity. Predicted to be involved in activation of GTPase activity. Predicted to act upstream of or within Ral protein signal transduction; regulation of exocyst localization; and regulation of protein localization. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), RALGAPB. . Gene score misZ 3.1771 (greater than the threshold 3.09). Trascript score misZ 4.2843 (greater than threshold 3.09). GenCC has associacion of gene with complex neurodevelopmental disorder.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RALGAPB | NM_020336.4 | c.2324G>A | p.Arg775His | missense_variant | 16/30 | ENST00000262879.11 | NP_065069.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RALGAPB | ENST00000262879.11 | c.2324G>A | p.Arg775His | missense_variant | 16/30 | 1 | NM_020336.4 | ENSP00000262879.6 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461816Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727218
GnomAD4 exome
AF:
AC:
4
AN:
1461816
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
727218
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
.;T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;.;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;L;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
1.0, 1.0
.;D;D;D
Vest4
MutPred
0.26
.;Loss of MoRF binding (P = 0.0145);Loss of MoRF binding (P = 0.0145);.;
MVP
MPC
1.4
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at