Variant X-118975381-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001031855.3(LONRF3):c.601G>C(p.Ala201Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000473 in 1,205,545 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 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: 𝑓 0.00029 ( 0 hom., 7 hem., cov: 24)

Exomes 𝑓: 0.000022 ( 0 hom. 6 hem. )

Consequence

LONRF3
NM_001031855.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.703

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029723227).

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LONRF3	NM_001031855.3 linkuse as main transcript	c.601G>C	p.Ala201Pro	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.601G>C	p.Ala201Pro	missense_variant	1/11	1	NM_001031855.3	ENSP00000360690.3	Q496Y0-1
LONRF3	ENST00000304778.11 linkuse as main transcript	c.601G>C	p.Ala201Pro	missense_variant	1/10	1		ENSP00000307732.7	Q496Y0-2
LONRF3	ENST00000439603.5 linkuse as main transcript	c.19G>C	p.Ala7Pro	missense_variant	1/10	1		ENSP00000414519.1	H0Y7Q8
LONRF3	ENST00000481285.5 linkuse as main transcript	n.601G>C		non_coding_transcript_exon_variant	1/11	2		ENSP00000435426.1	Q496Y0-3

Frequencies

GnomAD3 genomes

AF:

0.000292

AC:

AN:

113031

Hom.:

Cov.:

AF XY:

0.000170

AC XY:

AN XY:

35209

show subpopulations

Gnomad AFR

AF:

0.00103

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000920

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

GnomAD3 exomes

AF:

0.0000864

AC:

AN:

162036

Hom.:

AF XY:

0.0000708

AC XY:

AN XY:

56534

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.0000379

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:

0.00

Gnomad OTH exome

AF:

0.000247

GnomAD4 exome

AF:

0.0000220

AC:

AN:

1092471

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

359689

show subpopulations

Gnomad4 AFR exome

AF:

0.000689

Gnomad4 AMR exome

AF:

0.0000574

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:

0.00000357

Gnomad4 OTH exome

AF:

0.0000218

GnomAD4 genome

AF:

0.000292

AC:

AN:

113074

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

AN XY:

35264

show subpopulations

Gnomad4 AFR

AF:

0.00102

Gnomad4 AMR

AF:

0.0000919

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:

0.000230

ESP6500AA

AF:

0.000528

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000100

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

Mar 11, 2024

The c.601G>C (p.A201P) alteration is located in exon 1 (coding exon 1) of the LONRF3 gene. This alteration results from a G to C substitution at nucleotide position 601, causing the alanine (A) at amino acid position 201 to be replaced by a proline (P). 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

0.14

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.57

DEOGEN2

Benign

0.010

.;T

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.67

T;T

M_CAP

Pathogenic

0.60

MetaRNN

Benign

0.030

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.49

N;N

REVEL

Benign

0.26

Sift

Benign

0.24

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.0030

B;B

Vest4

0.29

MVP

0.72

MPC

0.85

ClinPred

0.0038

GERP RS

0.23

Varity_R

0.092

gMVP

0.61

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