2-86612177-T-C
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_005667.4(RNF103):āc.464A>Gā(p.Asn155Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000685 in 1,459,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000069 ( 0 hom. )
Consequence
RNF103
NM_005667.4 missense
NM_005667.4 missense
Scores
3
3
13
Clinical Significance
Conservation
PhyloP100: 5.93
Genes affected
RNF103 (HGNC:12859): (ring finger protein 103) The protein encoded by this gene contains a RING-H2 finger, a motif known to be involved in protein-protein and protein-DNA interactions. This gene is highly expressed in normal cerebellum, but not in the cerebral cortex. The expression of the rat counterpart in the frontal cortex and hippocampus was shown to be induced by elctroconvulsive treatment (ECT) as well as chronic antidepressant treatment, suggesting that this gene may be a molecular target for ECT and antidepressants. The protein is a ubiquitin ligase that functions in the endoplasmic reticulum-associated degradation pathway. Alternative splicing of this gene results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream CHMP3 (charged multivesicular body protein 3) gene. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.36283684).
BS2
High AC in GnomAdExome4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNF103 | NM_005667.4 | c.464A>G | p.Asn155Ser | missense_variant | 3/4 | ENST00000237455.5 | |
RNF103-CHMP3 | NM_001198954.1 | c.132+8153A>G | intron_variant | ||||
CHMP3-AS1 | NR_183900.1 | n.254-4999T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNF103 | ENST00000237455.5 | c.464A>G | p.Asn155Ser | missense_variant | 3/4 | 1 | NM_005667.4 | P1 | |
CHMP3-AS1 | ENST00000439077.1 | n.249-4999T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.0000442 AC: 11AN: 248964Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134522
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GnomAD4 exome AF: 0.00000685 AC: 10AN: 1459016Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 725708
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GnomAD4 genome Cov.: 32
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32
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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 | Jan 23, 2024 | The c.464A>G (p.N155S) alteration is located in exon 3 (coding exon 3) of the RNF103 gene. This alteration results from a A to G substitution at nucleotide position 464, causing the asparagine (N) at amino acid position 155 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
D
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of disorder (P = 0.0306);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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