Variant X-118975022-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001031855.3(LONRF3):c.242G>A(p.Gly81Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000512 in 1,172,447 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., 0 hem., cov: 25)

Exomes 𝑓: 0.0000047 ( 0 hom. 1 hem. )

Consequence

LONRF3
NM_001031855.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.86

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LONRF3	NM_001031855.3 linkuse as main transcript	c.242G>A	p.Gly81Glu	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.242G>A	p.Gly81Glu	missense_variant	1/11	1	NM_001031855.3	ENSP00000360690.3	Q496Y0-1
LONRF3	ENST00000304778.11 linkuse as main transcript	c.242G>A	p.Gly81Glu	missense_variant	1/10	1		ENSP00000307732.7	Q496Y0-2
LONRF3	ENST00000481285.5 linkuse as main transcript	n.242G>A		non_coding_transcript_exon_variant	1/11	2		ENSP00000435426.1	Q496Y0-3

Frequencies

GnomAD3 genomes

AF:

0.00000881

AC:

AN:

113519

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35645

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000176

AC:

AN:

113684

Hom.:

AF XY:

0.00

AC XY:

AN XY:

37876

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000460

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000472

AC:

AN:

1058928

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

345028

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000608

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000881

AC:

AN:

113519

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35645

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000187

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000912

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Sep 07, 2022

Gene of Uncertain Significance -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Uncertain

0.085

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

.;T

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.82

T;T

M_CAP

Pathogenic

0.81

MetaRNN

Uncertain

0.58

D;D

MetaSVM

Uncertain

0.21

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.3

D;D

REVEL

Uncertain

0.61

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.012

D;D

Polyphen

1.0

D;D

Vest4

0.16

MutPred

0.51

Loss of methylation at R80 (P = 0.0298);Loss of methylation at R80 (P = 0.0298);

MVP

0.62

MPC

1.3

ClinPred

0.79

GERP RS

3.0

Varity_R

0.61

gMVP

0.63

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