chr4-140868371-C-G

Position:

• chr4-140868371-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020724.2(RNF150):​c.1207G>C​(p.Glu403Gln) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF150 NM_020724.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.57

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 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=0.13836658).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF150	NM_020724.2	c.1207G>C	p.Glu403Gln	missense_variant	7/7	ENST00000515673.7	NP_065775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF150	ENST00000515673.7	c.1207G>C	p.Glu403Gln	missense_variant	7/7	5	NM_020724.2	ENSP00000425840.1
RNF150	ENST00000306799.7	c.1081G>C	p.Glu361Gln	missense_variant	7/7	1		ENSP00000304321.3
RNF150	ENST00000420921.6	c.784G>C	p.Glu262Gln	missense_variant	8/8	2		ENSP00000394581.2
RNF150	ENST00000506101.2	c.700G>C	p.Glu234Gln	missense_variant	8/8	5		ENSP00000425947.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.1207G>C (p.E403Q) alteration is located in exon 7 (coding exon 7) of the RNF150 gene. This alteration results from a G to C substitution at nucleotide position 1207, causing the glutamic acid (E) at amino acid position 403 to be replaced by a glutamine (Q). 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	0.080
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.0035	T;.;.
Eigen	Benign	-0.15
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.23	N;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.27	N;N;N
REVEL	Benign	0.18
Sift	Benign	0.74	T;T;T
Sift4G	Benign	0.64	T;T;T
Polyphen		0.034	B;B;.
Vest4		0.37
MutPred		0.18		Loss of phosphorylation at S400 (P = 0.1552);.;.;
MVP		0.32
MPC		0.54
ClinPred		0.88	D
GERP RS		5.7
Varity_R		0.094
gMVP		0.24

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: chr4-141789525;