16-1967753-G-C

Variant names:

• chr16-1967753-G-C
• NM_174903.6:c.178G>C

Variant summary

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

The NM_174903.6(RNF151):​c.178G>C​(p.Glu60Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNF151 NM_174903.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.09

Genes affected

RNF151 (HGNC:23235): (ring finger protein 151) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein ubiquitination. Predicted to be located in cytoplasm and nucleus. [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=0.16372731).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF151	NM_174903.6	c.178G>C	p.Glu60Gln	missense_variant	Exon 3 of 4	ENST00000569714.6	NP_777563.2
RNF151	XM_005255129.5	c.205G>C	p.Glu69Gln	missense_variant	Exon 3 of 4		XP_005255186.1
RNF151	NM_001348711.2	c.150-120G>C		intron_variant	Intron 2 of 3		NP_001335640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF151	ENST00000569714.6	c.178G>C	p.Glu60Gln	missense_variant	Exon 3 of 4	1	NM_174903.6	ENSP00000456566.1
RNF151	ENST00000321392.4	c.175G>C	p.Glu59Gln	missense_variant	Exon 2 of 3	1		ENSP00000325794.3
RNF151	ENST00000569210.6	c.150-120G>C		intron_variant	Intron 2 of 3	2		ENSP00000454886.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 17, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.178G>C (p.E60Q) alteration is located in exon 3 (coding exon 3) of the RNF151 gene. This alteration results from a G to C substitution at nucleotide position 178, causing the glutamic acid (E) at amino acid position 60 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	0.12
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.0027	T;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.51	T;T
M_CAP	Uncertain	0.099	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.56	N;N
REVEL	Benign	0.19
Sift	Benign	0.26	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.022	B;.
Vest4		0.23
MutPred		0.32		Gain of methylation at K59 (P = 0.1175);.;
MVP		0.78
MPC		0.18
ClinPred		0.21	T
GERP RS		3.8
Varity_R		0.084
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr16-2017754; COSMIC: COSV58399451; COSMIC: COSV58399451;