4-141132781-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_020724.2(RNF150):c.28T>C(p.Cys10Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF150 NM_020724.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.61

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04004857).
• BP6: Variant 4-141132781-A-G is Benign according to our data. Variant chr4-141132781-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2569508.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF150	NM_020724.2	c.28T>C	p.Cys10Arg	missense_variant	1/7	ENST00000515673.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF150	ENST00000515673.7	c.28T>C	p.Cys10Arg	missense_variant	1/7	5	NM_020724.2	P1
RNF150	ENST00000507500.5	c.28T>C	p.Cys10Arg	missense_variant	1/6	1
RNF150	ENST00000306799.7	c.28T>C	p.Cys10Arg	missense_variant	1/7	1
RNF150	ENST00000420921.6	c.-5-79050T>C		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.015
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	19
Dann	Benign	0.87
DEOGEN2	Benign	0.0058	T;.;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.040	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.3	N;N;N
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	1.6	N;N;N
REVEL	Benign	0.051
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.14
MutPred		0.49		Gain of disorder (P = 0.0191);Gain of disorder (P = 0.0191);Gain of disorder (P = 0.0191);
MVP		0.12
MPC		0.96
ClinPred		0.10	T
GERP RS		1.7
Varity_R		0.15
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-142053935; COSMIC: COSV60793626;