4-140868376-T-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.1202A>C(p.Glu401Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000104 in 1,446,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.000010 (0 hom.)
• Consequence: RNF150 NM_020724.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.05

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=0.12938532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF150	NM_020724.2	c.1202A>C	p.Glu401Ala	missense_variant	7/7	ENST00000515673.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF150	ENST00000515673.7	c.1202A>C	p.Glu401Ala	missense_variant	7/7	5	NM_020724.2	P1
RNF150	ENST00000306799.7	c.1076A>C	p.Glu359Ala	missense_variant	7/7	1
RNF150	ENST00000420921.6	c.779A>C	p.Glu260Ala	missense_variant	8/8	2
RNF150	ENST00000506101.2	c.695A>C	p.Glu232Ala	missense_variant	8/8	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000104 AC: 15 AN: 1446302 Hom.: 0 Cov.: 26 AF XY: 0.0000125 AC XY: 9 AN XY: 720664

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: 0.0000137

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

Dec 16, 2021

The c.1202A>C (p.E401A) alteration is located in exon 7 (coding exon 7) of the RNF150 gene. This alteration results from a A to C substitution at nucleotide position 1202, causing the glutamic acid (E) at amino acid position 401 to be replaced by an alanine (A). 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	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.049	T;.;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.021
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	T;T;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.;.
MutationTaster	Benign	0.98	D;D;D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.035
Sift	Uncertain	0.018	D;D;D
Sift4G	Benign	0.19	T;T;T
Polyphen		0.063	B;B;.
Vest4		0.21
MutPred		0.29		Loss of disorder (P = 0.0662);.;.;
MVP		0.36
MPC		0.67
ClinPred		0.83	D
GERP RS		4.5
Varity_R		0.11
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr4-141789530;