Variant X-118975168-A-G 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.388A>G(p.Ser130Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000562 in 1,174,103 control chromosomes in the GnomAD database, including 1 homozygotes. There are 23 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 0.000071 ( 0 hom., 3 hem., cov: 24)

Exomes 𝑓: 0.000055 ( 1 hom. 20 hem. )

Consequence

LONRF3
NM_001031855.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.351

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=0.017149985).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LONRF3	NM_001031855.3 linkuse as main transcript	c.388A>G	p.Ser130Gly	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.388A>G	p.Ser130Gly	missense_variant	1/11	1	NM_001031855.3	ENSP00000360690.3	Q496Y0-1
LONRF3	ENST00000304778.11 linkuse as main transcript	c.388A>G	p.Ser130Gly	missense_variant	1/10	1		ENSP00000307732.7	Q496Y0-2
LONRF3	ENST00000481285.5 linkuse as main transcript	n.388A>G		non_coding_transcript_exon_variant	1/11	2		ENSP00000435426.1	Q496Y0-3

Frequencies

GnomAD3 genomes

AF:

0.0000708

AC:

AN:

112923

Hom.:

Cov.:

AF XY:

0.0000854

AC XY:

AN XY:

35111

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000734

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:

0.000373

AC:

AN:

112715

Hom.:

AF XY:

0.000419

AC XY:

AN XY:

38175

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00188

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:

0.0000238

Gnomad OTH exome

AF:

0.000933

GnomAD4 exome

AF:

0.0000547

AC:

AN:

1061135

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

346129

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00186

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:

0.00000243

Gnomad4 OTH exome

AF:

0.0000448

GnomAD4 genome

AF:

0.0000708

AC:

AN:

112968

Hom.:

Cov.:

AF XY:

0.0000853

AC XY:

AN XY:

35166

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000733

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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000575

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

Oct 08, 2024

The c.388A>G (p.S130G) alteration is located in exon 1 (coding exon 1) of the LONRF3 gene. This alteration results from a A to G substitution at nucleotide position 388, causing the serine (S) at amino acid position 130 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

0.052

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.35

DANN

Benign

0.74

DEOGEN2

Benign

0.0053

.;T

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.37

T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.017

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.14

N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.17

N;N

REVEL

Benign

0.12

Sift

Benign

0.45

T;T

Sift4G

Benign

0.76

T;T

Polyphen

0.0

B;B

Vest4

0.017

MutPred

0.27

Loss of glycosylation at S130 (P = 5e-04);Loss of glycosylation at S130 (P = 5e-04);

MVP

0.53

MPC

0.35

ClinPred

0.019

GERP RS

-6.7

Varity_R

0.031

gMVP

0.24

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