Genetic Variant RNF112:p.Leu42Ile (chr17-19412526-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_007148.5(RNF112):c.124C>A(p.Leu42Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,613,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

RNF112
NM_007148.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

Publications

0 publications found

Variant links:

Genes affected

RNF112 (HGNC:12968): (ring finger protein 112) This gene encodes a member of the RING finger protein family of transcription factors. The protein is primarily expressed in brain. The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

RNF112 links:

ENSG00000265126 (HGNC:58560):

ENSG00000265126 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.19185346).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007148.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF112	NM_007148.5	MANE Select	c.124C>A	p.Leu42Ile	missense	Exon 3 of 14	NP_009079.2	Q9ULX5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF112	ENST00000461366.2	TSL:1 MANE Select	c.124C>A	p.Leu42Ile	missense	Exon 3 of 14	ENSP00000454919.1	Q9ULX5-1
RNF112	ENST00000908744.1		c.124C>A	p.Leu42Ile	missense	Exon 4 of 15	ENSP00000578803.1
RNF112	ENST00000908743.1		c.124C>A	p.Leu42Ile	missense	Exon 4 of 15	ENSP00000578802.1

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000206

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000653

AC:

AN:

244960

AF XY:

0.0000825

show subpopulations

Gnomad AFR exome

AF:

0.000196

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:

0.000119

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000190

AC:

278

AN:

1461214

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

119

AN XY:

726886

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000237

AC:

264

AN:

1111764

Other (OTH)

AF:

0.000215

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000132

AC:

AN:

152068

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41408

American (AMR)

AF:

0.0000655

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.000158

Hom.:

Bravo

AF:

0.000128

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000260

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.0000414

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Benign

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.75

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.19

MutationAssessor

Benign

1.0

PhyloP100

1.3

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.38

Sift

Pathogenic

0.0

Sift4G

Benign

0.12

Polyphen

0.98

Vest4

0.39

MVP

0.80

MPC

0.97

GERP RS

3.8

Varity_R

0.23

gMVP

0.12

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

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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