chr16-1968578-C-T

Variant names:

• chr16-1968578-C-T
• rs755327869
• NM_174903.6:c.391C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174903.6(RNF151):​c.391C>T​(p.Arg131Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000544 in 1,600,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: RNF151 NM_174903.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.876
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19037873).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174903.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF151	NM_174903.6	MANE Select	c.391C>T	p.Arg131Trp	missense	Exon 4 of 4	NP_777563.2
	RNF151	NM_001348711.2		c.*151C>T		3_prime_UTR	Exon 4 of 4	NP_001335640.1	H3BNJ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF151	ENST00000569714.6	TSL:1 MANE Select	c.391C>T	p.Arg131Trp	missense	Exon 4 of 4	ENSP00000456566.1	Q2KHN1
	RNF151	ENST00000321392.4	TSL:1	c.388C>T	p.Arg130Trp	missense	Exon 3 of 3	ENSP00000325794.3	A0A0C4DFQ4
	RNF151	ENST00000569210.6	TSL:2	c.*151C>T		3_prime_UTR	Exon 4 of 4	ENSP00000454886.1	H3BNJ8

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152218 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000367 AC: 8 AN: 218164 AF XY: 0.0000166

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000618

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000631

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000552 AC: 80 AN: 1448398 Hom.: 0 Cov.: 32 AF XY: 0.0000556 AC XY: 40 AN XY: 719490

African (AFR) AF: 0.0000605 AC: 2 AN: 33032

American (AMR) AF: 0.0000229 AC: 1 AN: 43658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25888

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38742

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50910

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5728

European-Non Finnish (NFE) AF: 0.0000651 AC: 72 AN: 1106614

Other (OTH) AF: 0.0000334 AC: 2 AN: 59816

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152218 Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74370

African (AFR) AF: 0.0000241 AC: 1 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000158 Hom.: 0

Bravo AF: 0.0000416

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.0000585 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.88
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.029
Sift	Benign	0.041	D
Sift4G	Uncertain	0.025	D
Polyphen		1.0	D
Vest4		0.17
MutPred		0.43		Loss of glycosylation at T126 (P = 0.1036)
MVP		0.52
MPC		0.19
ClinPred		0.38	T
GERP RS		-0.45
Varity_R		0.051
gMVP		0.74
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs755327869; hg19: chr16-2018579; COSMIC: COSV58400717; COSMIC: COSV58400717;