chr3-49718412-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_198722.3(AMIGO3):āc.1054T>Gā(p.Cys352Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,612,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Exomes š: 0.000016 ( 0 hom. )
Consequence
AMIGO3
NM_198722.3 missense
NM_198722.3 missense
Scores
12
5
2
Clinical Significance
Conservation
PhyloP100: 4.43
Genes affected
AMIGO3 (HGNC:24075): (adhesion molecule with Ig like domain 3) Predicted to be involved in brain development and heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules. Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
RNF123 (HGNC:21148): (ring finger protein 123) The protein encoded by this gene contains a C-terminal RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions, and an N-terminal SPRY domain. This protein displays E3 ubiquitin ligase activity toward the cyclin-dependent kinase inhibitor 1B which is also known as p27 or KIP1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
GMPPB (HGNC:22932): (GDP-mannose pyrophosphorylase B) This gene is thought to encode a GDP-mannose pyrophosphorylase. The encoded protein catalyzes the conversion of mannose-1-phosphate and GTP to GDP-mannose, a reaction involved in the production of N-linked oligosaccharides. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jan 2009]
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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;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.801
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AMIGO3 | NM_198722.3 | c.1054T>G | p.Cys352Gly | missense_variant | 1/1 | ENST00000320431.8 | |
RNF123 | NM_022064.5 | c.3500+1935A>C | intron_variant | ENST00000327697.11 | |||
RNF123 | NR_135218.2 | n.3826+1935A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMIGO3 | ENST00000320431.8 | c.1054T>G | p.Cys352Gly | missense_variant | 1/1 | NM_198722.3 | P1 | ||
RNF123 | ENST00000327697.11 | c.3500+1935A>C | intron_variant | 1 | NM_022064.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000360 AC: 9AN: 249888Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135472
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1460692Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 726680
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74380
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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 | May 16, 2024 | The c.1054T>G (p.C352G) alteration is located in exon 1 (coding exon 1) of the AMIGO3 gene. This alteration results from a T to G substitution at nucleotide position 1054, causing the cysteine (C) at amino acid position 352 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of stability (P = 0.0059);
MVP
ClinPred
D
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