Variant 4-141132363-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020724.2(RNF150):c.446G>A(p.Gly149Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000131 in 1,595,048 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 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

RNF150
NM_020724.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.99

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028198391).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF150	NM_020724.2 link	c.446G>A	p.Gly149Asp	missense_variant	1/7	ENST00000515673.7	NP_065775.1	Q9ULK6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF150	ENST00000515673.7 link	c.446G>A	p.Gly149Asp	missense_variant	1/7	5	NM_020724.2	ENSP00000425840.1		Q9ULK6-1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

151904

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000216

AC:

AN:

217402

Hom.:

AF XY:

0.000214

AC XY:

AN XY:

116750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000294

Gnomad ASJ exome

AF:

0.000107

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000150

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000330

Gnomad OTH exome

AF:

0.000182

GnomAD4 exome

AF:

0.000132

AC:

190

AN:

1443026

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

AN XY:

715712

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000290

Gnomad4 ASJ exome

AF:

0.000195

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000846

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000124

Gnomad4 OTH exome

AF:

0.000268

GnomAD4 genome

AF:

0.000125

AC:

AN:

152022

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.000200

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.000248

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

Nov 26, 2024

The c.446G>A (p.G149D) alteration is located in exon 1 (coding exon 1) of the RNF150 gene. This alteration results from a G to A substitution at nucleotide position 446, causing the glycine (G) at amino acid position 149 to be replaced by an aspartic acid (D). 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

Uncertain

0.54

BayesDel_addAF

Benign

-0.054

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

T;.;.

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.47

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.028

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.3

L;L;L

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.4

N;N;N

REVEL

Uncertain

0.40

Sift

Benign

0.54

T;T;T

Sift4G

Benign

0.59

T;T;T

Polyphen

0.60

P;P;B

Vest4

0.85

MutPred

0.42

Gain of catalytic residue at G149 (P = 0.0022);Gain of catalytic residue at G149 (P = 0.0022);Gain of catalytic residue at G149 (P = 0.0022);

MVP

0.34

MPC

1.7

ClinPred

0.13

GERP RS

4.8

Varity_R

0.37

gMVP

0.81

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