X-118975100-T-C
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_001031855.3(LONRF3):āc.320T>Cā(p.Leu107Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000615 in 1,170,575 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000018 ( 0 hom., 0 hem., cov: 25)
Exomes š: 0.000066 ( 0 hom. 22 hem. )
Consequence
LONRF3
NM_001031855.3 missense
NM_001031855.3 missense
Scores
9
4
4
Clinical Significance
Conservation
PhyloP100: 6.69
Genes affected
LONRF3 (HGNC:21152): (LON peptidase N-terminal domain and ring finger 3) The protein encoded by this gene contains a 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. Multiple alternatively spliced transcript variants have been suggested, but their full length natures are not clear. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.87
BS2
High Hemizygotes in GnomAdExome4 at 22 gene
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LONRF3 | ENST00000371628.8 | c.320T>C | p.Leu107Pro | missense_variant | 1/11 | 1 | NM_001031855.3 | ENSP00000360690.3 | ||
LONRF3 | ENST00000304778.11 | c.320T>C | p.Leu107Pro | missense_variant | 1/10 | 1 | ENSP00000307732.7 | |||
LONRF3 | ENST00000481285.5 | n.320T>C | non_coding_transcript_exon_variant | 1/11 | 2 | ENSP00000435426.1 |
Frequencies
GnomAD3 genomes AF: 0.0000177 AC: 2AN: 113084Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0AN XY: 35248
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GnomAD3 exomes AF: 0.0000274 AC: 3AN: 109479Hom.: 0 AF XY: 0.0000527 AC XY: 2AN XY: 37917
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GnomAD4 exome AF: 0.0000662 AC: 70AN: 1057491Hom.: 0 Cov.: 34 AF XY: 0.0000638 AC XY: 22AN XY: 344875
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GnomAD4 genome AF: 0.0000177 AC: 2AN: 113084Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0AN XY: 35248
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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 | Aug 10, 2024 | The c.320T>C (p.L107P) alteration is located in exon 1 (coding exon 1) of the LONRF3 gene. This alteration results from a T to C substitution at nucleotide position 320, causing the leucine (L) at amino acid position 107 to be replaced by a proline (P). 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
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MVP
MPC
1.5
ClinPred
D
GERP RS
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