4-141132654-G-A

Position:

• chr4-141132654-G-A

Variant summary

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

The NM_020724.2(RNF150):​c.155C>T​(p.Ala52Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,336 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RNF150 NM_020724.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.885

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060432464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF150	NM_020724.2	c.155C>T	p.Ala52Val	missense_variant	1/7	ENST00000515673.7	NP_065775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF150	ENST00000515673.7	c.155C>T	p.Ala52Val	missense_variant	1/7	5	NM_020724.2	ENSP00000425840.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450336 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 721356

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.00

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

Nov 20, 2024

The c.155C>T (p.A52V) 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 155, causing the alanine (A) at amino acid position 52 to be replaced by a valine (V). 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	0.077
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.0080	T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.60	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.060	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.0	L;L;L
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.23	N;N;N
REVEL	Benign	0.012
Sift	Benign	0.40	T;T;T
Sift4G	Benign	0.30	T;T;T
Polyphen		0.029	B;B;B
Vest4		0.14
MutPred		0.30		Gain of catalytic residue at A52 (P = 0.0576);Gain of catalytic residue at A52 (P = 0.0576);Gain of catalytic residue at A52 (P = 0.0576);
MVP		0.15
MPC		0.54
ClinPred		0.042	T
GERP RS		-0.77
Varity_R		0.051
gMVP		0.39

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: chr4-142053808; COSMIC: COSV60800154;