Variant X-118974895-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001031855.3(LONRF3):c.115C>A(p.Pro39Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000885 in 113,016 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

LONRF3
NM_001031855.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66

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]

LONRF3 links:

LONRF3 (HGNC:):

LONRF3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13048011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LONRF3	NM_001031855.3 linkuse as main transcript	c.115C>A	p.Pro39Thr	missense_variant	1/11	ENST00000371628.8	NP_001027026.1	Q496Y0-1A8K2D3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LONRF3	ENST00000371628.8 linkuse as main transcript	c.115C>A	p.Pro39Thr	missense_variant	1/11	1	NM_001031855.3	ENSP00000360690.3	Q496Y0-1
LONRF3	ENST00000304778.11 linkuse as main transcript	c.115C>A	p.Pro39Thr	missense_variant	1/10	1		ENSP00000307732.7	Q496Y0-2
LONRF3	ENST00000481285.5 linkuse as main transcript	n.115C>A		non_coding_transcript_exon_variant	1/11	2		ENSP00000435426.1	Q496Y0-3

Frequencies

GnomAD3 genomes

AF:

0.00000885

AC:

AN:

113016

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35160

show subpopulations

Gnomad AFR

AF:

0.0000321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1083613

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

352471

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000885

AC:

AN:

113016

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35160

show subpopulations

Gnomad4 AFR

AF:

0.0000321

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000834

AC:

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 09, 2021

The c.115C>A (p.P39T) alteration is located in exon 1 (coding exon 1) of the LONRF3 gene. This alteration results from a C to A substitution at nucleotide position 115, causing the proline (P) at amino acid position 39 to be replaced by a threonine (T). 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

0.072

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.010

.;T

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.73

T;T

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.74

N;N

REVEL

Benign

0.13

Sift

Uncertain

0.019

D;D

Sift4G

Benign

0.35

T;T

Polyphen

0.020

B;B

Vest4

0.12

MutPred

0.19

Gain of phosphorylation at P39 (P = 0.0248);Gain of phosphorylation at P39 (P = 0.0248);

MVP

0.72

MPC

0.47

ClinPred

0.065

GERP RS

2.8

Varity_R

0.079

gMVP

0.20

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over