chrX-118975175-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001031855.3(LONRF3):​c.395C>G​(p.Ala132Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,062,727 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)
Exomes 𝑓: 0.000012 ( 0 hom. 8 hem. )

Consequence

LONRF3
NM_001031855.3 missense

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0200
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.042517334).
BS2
High Hemizygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LONRF3NM_001031855.3 linkc.395C>G p.Ala132Gly missense_variant Exon 1 of 11 ENST00000371628.8 NP_001027026.1 Q496Y0-1A8K2D3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LONRF3ENST00000371628.8 linkc.395C>G p.Ala132Gly missense_variant Exon 1 of 11 1 NM_001031855.3 ENSP00000360690.3 Q496Y0-1
LONRF3ENST00000304778.11 linkc.395C>G p.Ala132Gly missense_variant Exon 1 of 10 1 ENSP00000307732.7 Q496Y0-2
LONRF3ENST00000481285.5 linkn.395C>G non_coding_transcript_exon_variant Exon 1 of 11 2 ENSP00000435426.1 Q496Y0-3
LONRF3ENST00000439603.5 linkc.-188C>G upstream_gene_variant 1 ENSP00000414519.1 H0Y7Q8

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD3 exomes
AF:
0.0000524
AC:
6
AN:
114558
Hom.:
0
AF XY:
0.000105
AC XY:
4
AN XY:
38006
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000413
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000122
AC:
13
AN:
1062727
Hom.:
0
Cov.:
34
AF XY:
0.0000231
AC XY:
8
AN XY:
346357
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000256
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
24
ExAC
AF:
0.0000568
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.395C>G (p.A132G) alteration is located in exon 1 (coding exon 1) of the LONRF3 gene. This alteration results from a C to G substitution at nucleotide position 395, causing the alanine (A) at amino acid position 132 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
5.3
DANN
Benign
0.83
DEOGEN2
Benign
0.0065
.;T
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.42
T;T
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.043
T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.81
L;L
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-0.30
N;N
REVEL
Benign
0.15
Sift
Benign
0.26
T;T
Sift4G
Benign
0.49
T;T
Polyphen
0.0
B;B
Vest4
0.040
MutPred
0.25
Gain of relative solvent accessibility (P = 0.0104);Gain of relative solvent accessibility (P = 0.0104);
MVP
0.55
MPC
0.38
ClinPred
0.021
T
GERP RS
0.12
Varity_R
0.046
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs768753376; hg19: chrX-118109138; API