dbSNP rs976953628: LONRF3:p.Leu107Pro (chrX-118975100-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001031855.3(LONRF3):c.320T>C(p.Leu107Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000615 in 1,170,575 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 25)

Exomes 𝑓: 0.000066 ( 0 hom. 22 hem. )

Consequence

LONRF3
NM_001031855.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.69

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.87

BS2

High Hemizygotes in GnomAdExome4 at 22 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031855.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LONRF3	NM_001031855.3	MANE Select	c.320T>C	p.Leu107Pro	missense	Exon 1 of 11	NP_001027026.1	Q496Y0-1
LONRF3	NM_024778.5		c.320T>C	p.Leu107Pro	missense	Exon 1 of 10	NP_079054.3	A8K2D3
LONRF3	NR_110311.1		n.487T>C		non_coding_transcript_exon	Exon 1 of 11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LONRF3	ENST00000371628.8	TSL:1 MANE Select	c.320T>C	p.Leu107Pro	missense	Exon 1 of 11	ENSP00000360690.3	Q496Y0-1
LONRF3	ENST00000304778.11	TSL:1	c.320T>C	p.Leu107Pro	missense	Exon 1 of 10	ENSP00000307732.7	Q496Y0-2
LONRF3	ENST00000961937.1		c.320T>C	p.Leu107Pro	missense	Exon 1 of 10	ENSP00000631996.1

Frequencies

GnomAD3 genomes

AF:

0.0000177

AC:

AN:

113084

Hom.:

Cov.:

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000274

AC:

AN:

109479

AF XY:

0.0000527

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000735

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000662

AC:

AN:

1057491

Hom.:

Cov.:

AF XY:

0.0000638

AC XY:

AN XY:

344875

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25146

American (AMR)

AF:

0.00

AC:

AN:

28693

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18670

East Asian (EAS)

AF:

0.00

AC:

AN:

27419

South Asian (SAS)

AF:

0.00

AC:

AN:

50153

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36812

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3739

European-Non Finnish (NFE)

AF:

0.0000815

AC:

AN:

822356

Other (OTH)

AF:

0.0000674

AC:

AN:

44503

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000177

AC:

AN:

113084

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31214

American (AMR)

AF:

0.00

AC:

AN:

10888

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3545

South Asian (SAS)

AF:

0.00

AC:

AN:

2799

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000376

AC:

AN:

53246

Other (OTH)

AF:

0.00

AC:

AN:

1531

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.46

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.75

M_CAP

Pathogenic

0.95

MetaRNN

Pathogenic

0.87

MetaSVM

Uncertain

0.40

MutationAssessor

Benign

0.90

PhyloP100

6.7

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.0

REVEL

Pathogenic

0.76

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.81

MVP

0.98

MPC

1.5

ClinPred

0.70

GERP RS

4.8

PromoterAI

-0.025

Neutral

(source)

Varity_R

0.90

gMVP

0.89

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over