Genetic Variant NM_001031855.3:c.68C>T (chrX-118974848-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001031855.3(LONRF3):c.68C>T(p.Ser23Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,206,679 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.000011 ( 0 hom. 5 hem. )

Consequence

LONRF3
NM_001031855.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.226

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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018008232).

BP6

Variant X-118974848-C-T is Benign according to our data. Variant chrX-118974848-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3119562.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 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.68C>T	p.Ser23Leu	missense	Exon 1 of 11	NP_001027026.1	Q496Y0-1
LONRF3	NM_024778.5		c.68C>T	p.Ser23Leu	missense	Exon 1 of 10	NP_079054.3	A8K2D3
LONRF3	NR_110311.1		n.235C>T		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.68C>T	p.Ser23Leu	missense	Exon 1 of 11	ENSP00000360690.3	Q496Y0-1
LONRF3	ENST00000304778.11	TSL:1	c.68C>T	p.Ser23Leu	missense	Exon 1 of 10	ENSP00000307732.7	Q496Y0-2
LONRF3	ENST00000961937.1		c.68C>T	p.Ser23Leu	missense	Exon 1 of 10	ENSP00000631996.1

Frequencies

GnomAD3 genomes

AF:

0.0000886

AC:

AN:

112846

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000321

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000596

AC:

AN:

167778

AF XY:

0.0000350

show subpopulations

Gnomad AFR exome

AF:

0.000842

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1093833

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

360137

show subpopulations

African (AFR)

AF:

0.000341

AC:

AN:

26359

American (AMR)

AF:

0.00

AC:

AN:

34850

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19301

East Asian (EAS)

AF:

0.00

AC:

AN:

30056

South Asian (SAS)

AF:

0.00

AC:

AN:

53264

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39313

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4126

European-Non Finnish (NFE)

AF:

0.00000357

AC:

AN:

840642

Other (OTH)

AF:

0.00

AC:

AN:

45922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000886

AC:

AN:

112846

Hom.:

Cov.:

AF XY:

0.0000571

AC XY:

AN XY:

35000

show subpopulations

African (AFR)

AF:

0.000321

AC:

AN:

31117

American (AMR)

AF:

0.00

AC:

AN:

10821

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3555

South Asian (SAS)

AF:

0.00

AC:

AN:

2752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6251

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53259

Other (OTH)

AF:

0.00

AC:

AN:

1514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00237

Hom.:

Bravo

AF:

0.000170

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000743

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

Benign

0.059

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.3

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.0092

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.67

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-2.1

PhyloP100

-0.23

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.33

REVEL

Benign

0.18

Sift

Benign

0.79

Sift4G

Benign

0.80

Polyphen

0.0

Vest4

0.032

MVP

0.59

MPC

0.34

ClinPred

0.0058

GERP RS

2.7

PromoterAI

-0.067

Neutral

(source)

Varity_R

0.041

gMVP

0.11

Mutation Taster

=99/1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over