Variant X-118975349-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000371628.8(LONRF3):c.569G>A(p.Arg190Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,095,558 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000027 ( 0 hom. 2 hem. )

Consequence

LONRF3
ENST00000371628.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11101127).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LONRF3	NM_001031855.3 linkuse as main transcript	c.569G>A	p.Arg190Gln	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.569G>A	p.Arg190Gln	missense_variant	1/11	1	NM_001031855.3	ENSP00000360690.3	Q496Y0-1
LONRF3	ENST00000304778.11 linkuse as main transcript	c.569G>A	p.Arg190Gln	missense_variant	1/10	1		ENSP00000307732.7	Q496Y0-2
LONRF3	ENST00000481285.5 linkuse as main transcript	n.569G>A		non_coding_transcript_exon_variant	1/11	2		ENSP00000435426.1	Q496Y0-3
LONRF3	ENST00000439603.5 linkuse as main transcript	c.-14G>A		upstream_gene_variant		1		ENSP00000414519.1	H0Y7Q8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000117

AC:

AN:

171638

Hom.:

AF XY:

0.0000159

AC XY:

AN XY:

62884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000751

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000135

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1095558

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

362104

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000832

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

May 18, 2023

The c.569G>A (p.R190Q) alteration is located in exon 1 (coding exon 1) of the LONRF3 gene. This alteration results from a G to A substitution at nucleotide position 569, causing the arginine (R) at amino acid position 190 to be replaced by a glutamine (Q). 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

0.20

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

.;T

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.86

D;D

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.95

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.29

N;N

REVEL

Benign

0.039

Sift

Benign

0.14

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.75

P;P

Vest4

0.10

MutPred

0.35

Loss of MoRF binding (P = 0.0263);Loss of MoRF binding (P = 0.0263);

MVP

0.27

MPC

1.3

ClinPred

0.34

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.094

gMVP

0.37

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