Variant 4-141132477-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020724.2(RNF150):c.332C>T(p.Pro111Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000205 in 1,608,574 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 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

RNF150
NM_020724.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.22

Variant links:

Genes affected

RNF150 (HGNC:23138): (ring finger protein 150) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in ubiquitin-dependent protein catabolic process. Predicted to be integral component of membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RNF150 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2522245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF150	NM_020724.2 linkuse as main transcript	c.332C>T	p.Pro111Leu	missense_variant	1/7	ENST00000515673.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF150	ENST00000515673.7 linkuse as main transcript	c.332C>T	p.Pro111Leu	missense_variant	1/7	5	NM_020724.2	P1	Q9ULK6-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000588

AC:

AN:

238170

Hom.:

AF XY:

0.0000621

AC XY:

AN XY:

128892

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000121

Gnomad OTH exome

AF:

0.000173

GnomAD4 exome

AF:

0.000216

AC:

314

AN:

1456418

Hom.:

Cov.:

AF XY:

0.000227

AC XY:

164

AN XY:

723896

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.000275

Gnomad4 OTH exome

AF:

0.0000831

GnomAD4 genome

AF:

0.000105

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000232

Hom.:

Bravo

AF:

0.0000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.0000495

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

May 24, 2023

The c.332C>T (p.P111L) alteration is located in exon 1 (coding exon 1) of the RNF150 gene. This alteration results from a C to T substitution at nucleotide position 332, causing the proline (P) at amino acid position 111 to be replaced by a leucine (L). 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

0.18

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.39

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Pathogenic

3.3

M;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-6.3

D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.014

D;D;D

Polyphen

1.0

D;D;P

Vest4

0.50

MVP

0.51

MPC

0.95

ClinPred

0.84

GERP RS

4.1

Varity_R

0.72

gMVP

0.66

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