Genetic Variant NM_174903.6:c.463C>A (chr16-1968650-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_174903.6(RNF151):c.463C>A(p.Arg155Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,413,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R155C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

RNF151
NM_174903.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0520

Publications

0 publications found

Variant links:

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]

RNF151 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.10836136).

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.463C>A	p.Arg155Ser	missense	Exon 4 of 4	NP_777563.2
	RNF151	NM_001348711.2		c.*223C>A		3_prime_UTR	Exon 4 of 4	NP_001335640.1	H3BNJ8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF151	ENST00000569714.6	TSL:1 MANE Select	c.463C>A	p.Arg155Ser	missense	Exon 4 of 4	ENSP00000456566.1	Q2KHN1
RNF151	ENST00000321392.4	TSL:1	c.460C>A	p.Arg154Ser	missense	Exon 3 of 3	ENSP00000325794.3	A0A0C4DFQ4
RNF151	ENST00000569210.6	TSL:2	c.*223C>A		3_prime_UTR	Exon 4 of 4	ENSP00000454886.1	H3BNJ8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.07e-7

AC:

AN:

1413874

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

699252

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32138

American (AMR)

AF:

0.00

AC:

AN:

37930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25350

East Asian (EAS)

AF:

0.00

AC:

AN:

36548

South Asian (SAS)

AF:

0.00

AC:

AN:

80880

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48246

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

9.19e-7

AC:

AN:

1088490

Other (OTH)

AF:

0.00

AC:

AN:

58586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.0084

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.50

M_CAP

Benign

0.012

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

0.052

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.5

REVEL

Benign

0.050

Sift

Benign

0.68

Sift4G

Benign

0.066

Polyphen

0.65

Vest4

0.15

MutPred

0.43

Loss of MoRF binding (P = 0.0415)

MVP

0.50

MPC

0.22

ClinPred

0.19

GERP RS

3.0

Varity_R

0.11

gMVP

0.73

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over