16-1967321-C-G

Variant names:

• chr16-1967321-C-G
• NM_174903.6:c.51C>G

Variant summary

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

The NM_174903.6(RNF151):​c.51C>G​(p.Asn17Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,330 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RNF151 NM_174903.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.419

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=0.12413475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF151	NM_174903.6	c.51C>G	p.Asn17Lys	missense_variant	Exon 2 of 4	ENST00000569714.6	NP_777563.2
RNF151	NM_001348711.2	c.51C>G	p.Asn17Lys	missense_variant	Exon 2 of 4		NP_001335640.1
RNF151	XM_005255129.5	c.78C>G	p.Asn26Lys	missense_variant	Exon 2 of 4		XP_005255186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF151	ENST00000569714.6	c.51C>G	p.Asn17Lys	missense_variant	Exon 2 of 4	1	NM_174903.6	ENSP00000456566.1
RNF151	ENST00000321392.4	c.48C>G	p.Asn16Lys	missense_variant	Exon 1 of 3	1		ENSP00000325794.3
RNF151	ENST00000569210.6	c.51C>G	p.Asn17Lys	missense_variant	Exon 2 of 4	2		ENSP00000454886.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461330 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726926

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.51C>G (p.N17K) alteration is located in exon 2 (coding exon 2) of the RNF151 gene. This alteration results from a C to G substitution at nucleotide position 51, causing the asparagine (N) at amino acid position 17 to be replaced by a lysine (K). 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	0.29
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.93
DEOGEN2	Benign	0.013	.;T;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.46	T;T;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.17	.;N;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.23
Sift	Benign	0.044	D;T;T
Sift4G	Benign	0.073	T;T;T
Polyphen		0.0040	.;B;.
Vest4		0.19
MutPred		0.41		Gain of methylation at N17 (P = 0.0044);Gain of methylation at N17 (P = 0.0044);.;
MVP		0.67
MPC		0.19
ClinPred		0.11	T
GERP RS		1.0
Varity_R		0.090
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr16-2017322;