dbSNP rs189943685: RNF151:p.Arg141Ser (chr16-1968608-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_174903.6(RNF151):c.421C>A(p.Arg141Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000021 in 1,426,938 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 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. R141C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RNF151
NM_174903.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.09

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
RNF151	NM_174903.6 link	c.421C>A	p.Arg141Ser	missense_variant	Exon 4 of 4	ENST00000569714.6	NP_777563.2
RNF151	XM_005255129.5 link	c.448C>A	p.Arg150Ser	missense_variant	Exon 4 of 4		XP_005255186.1
RNF151	NM_001348711.2 link	c.*181C>A		3_prime_UTR_variant	Exon 4 of 4		NP_001335640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RNF151	ENST00000569714.6 link	c.421C>A	p.Arg141Ser	missense_variant	Exon 4 of 4	1	NM_174903.6	ENSP00000456566.1	Q2KHN1
RNF151	ENST00000321392.4 link	c.418C>A	p.Arg140Ser	missense_variant	Exon 3 of 3	1		ENSP00000325794.3	A0A0C4DFQ4
RNF151	ENST00000569210.6 link	c.*181C>A		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000454886.1	H3BNJ8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1426938

Hom.:

Cov.:

AF XY:

0.00000424

AC XY:

AN XY:

706874

show subpopulations

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:

0.00000274

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0085

T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.20

Sift

Benign

0.17

T;T

Sift4G

Benign

0.063

T;T

Polyphen

0.92

P;.

Vest4

0.35

MutPred

0.45

Loss of catalytic residue at R141 (P = 0.1034);.;

MVP

0.50

MPC

0.38

ClinPred

0.61

GERP RS

3.3

Varity_R

0.13

gMVP

0.68

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over