15-52124541-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_016194.4(GNB5):c.1108G>A(p.Val370Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000446 in 1,613,804 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: 0.000045 ( 1 hom. )
Consequence
GNB5
NM_016194.4 missense
NM_016194.4 missense
Scores
1
3
14
Clinical Significance
Conservation
PhyloP100: 5.99
Genes affected
GNB5 (HGNC:4401): (G protein subunit beta 5) Heterotrimeric guanine nucleotide-binding proteins (G proteins), which integrate signals between receptors and effector proteins, are composed of an alpha, a beta, and a gamma subunit. These subunits are encoded by families of related genes. This gene encodes a beta subunit. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. Alternatively spliced transcript variants encoding different isoforms exist. [provided by RefSeq, Jul 2008]
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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=0.2358593).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNB5 | NM_016194.4 | c.1108G>A | p.Val370Ile | missense_variant | 12/13 | ENST00000261837.12 | |
GNB5 | NM_006578.4 | c.982G>A | p.Val328Ile | missense_variant | 10/11 | ||
GNB5 | NM_001379343.1 | c.826G>A | p.Val276Ile | missense_variant | 10/11 | ||
GNB5 | XM_011521162.4 | c.982G>A | p.Val328Ile | missense_variant | 10/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNB5 | ENST00000261837.12 | c.1108G>A | p.Val370Ile | missense_variant | 12/13 | 5 | NM_016194.4 | P3 | |
ENST00000557898.1 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152228Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000596 AC: 15AN: 251488Hom.: 0 AF XY: 0.0000956 AC XY: 13AN XY: 135920
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GnomAD4 exome AF: 0.0000452 AC: 66AN: 1461458Hom.: 1 Cov.: 30 AF XY: 0.0000688 AC XY: 50AN XY: 727080
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152346Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74504
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 27, 2020 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;B;.
Vest4
MutPred
Loss of methylation at R369 (P = 0.06);.;.;
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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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