chr19-3136473-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_002068.4(GNA15):c.23G>A(p.Arg8His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 1,551,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00021 ( 0 hom. )
Consequence
GNA15
NM_002068.4 missense
NM_002068.4 missense
Scores
1
15
Clinical Significance
Conservation
PhyloP100: -0.00100
Genes affected
GNA15 (HGNC:4383): (G protein subunit alpha 15) Enables G protein-coupled receptor binding activity. Involved in positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway. Predicted to be located in plasma membrane. Predicted to be part of heterotrimeric G-protein complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.055122167).
BS2
?
High AC in GnomAd at 40 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNA15 | NM_002068.4 | c.23G>A | p.Arg8His | missense_variant | 1/7 | ENST00000262958.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNA15 | ENST00000262958.4 | c.23G>A | p.Arg8His | missense_variant | 1/7 | 1 | NM_002068.4 | P1 | |
GNA15 | ENST00000592455.1 | c.23G>A | p.Arg8His | missense_variant, NMD_transcript_variant | 1/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000263 AC: 40AN: 152176Hom.: 0 Cov.: 31
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000202 AC: 32AN: 158230Hom.: 0 AF XY: 0.000238 AC XY: 20AN XY: 83874
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GnomAD4 exome AF: 0.000205 AC: 287AN: 1399560Hom.: 0 Cov.: 32 AF XY: 0.000209 AC XY: 144AN XY: 690572
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GnomAD4 genome ? AF: 0.000263 AC: 40AN: 152294Hom.: 0 Cov.: 31 AF XY: 0.000309 AC XY: 23AN XY: 74464
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ExAC
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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 | Oct 26, 2022 | The c.23G>A (p.R8H) alteration is located in exon 1 (coding exon 1) of the GNA15 gene. This alteration results from a G to A substitution at nucleotide position 23, causing the arginine (R) at amino acid position 8 to be replaced by a histidine (H). 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
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Vest4
MVP
MPC
ClinPred
T
GERP RS
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