17-76159533-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_052916.3(RNF157):c.1106T>G(p.Leu369Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000811 in 1,602,322 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
RNF157
NM_052916.3 missense
NM_052916.3 missense
Scores
11
5
3
Clinical Significance
Conservation
PhyloP100: 9.05
Genes affected
RNF157 (HGNC:29402): (ring finger protein 157) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in several processes, including negative regulation of signal transduction; positive regulation of dendrite extension; and protein autoubiquitination. Predicted to be located in cell body. Predicted to be active in early endosome; nucleus; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNF157 | NM_052916.3 | c.1106T>G | p.Leu369Arg | missense_variant | 12/19 | ENST00000269391.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNF157 | ENST00000269391.11 | c.1106T>G | p.Leu369Arg | missense_variant | 12/19 | 1 | NM_052916.3 | P4 | |
RNF157 | ENST00000647930.1 | c.1106T>G | p.Leu369Arg | missense_variant | 12/19 | A1 | |||
RNF157 | ENST00000319945.10 | c.1106T>G | p.Leu369Arg | missense_variant | 12/18 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152232Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000419 AC: 1AN: 238834Hom.: 0 AF XY: 0.00000771 AC XY: 1AN XY: 129660
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GnomAD4 exome AF: 0.00000345 AC: 5AN: 1450090Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2AN XY: 721584
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74382
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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 | Nov 03, 2023 | The c.1106T>G (p.L369R) alteration is located in exon 12 (coding exon 12) of the RNF157 gene. This alteration results from a T to G substitution at nucleotide position 1106, causing the leucine (L) at amino acid position 369 to be replaced by an arginine (R). 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
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;D
REVEL
Uncertain
Sift
Pathogenic
D;.;D
Sift4G
Pathogenic
D;.;D
Polyphen
D;.;D
Vest4
MutPred
Gain of methylation at L369 (P = 0.0387);Gain of methylation at L369 (P = 0.0387);Gain of methylation at L369 (P = 0.0387);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Score
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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