16-1968671-C-T

Variant summary

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

The NM_174903.6(RNF151):​c.484C>T​(p.Arg162Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000287 in 1,568,136 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

RNF151
NM_174903.6 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.30
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]

Genome browser will be placed here

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 UniProt
RNF151NM_174903.6 linkc.484C>T p.Arg162Trp missense_variant Exon 4 of 4 ENST00000569714.6 NP_777563.2
RNF151XM_005255129.5 linkc.511C>T p.Arg171Trp missense_variant Exon 4 of 4 XP_005255186.1
RNF151NM_001348711.2 linkc.*244C>T 3_prime_UTR_variant Exon 4 of 4 NP_001335640.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RNF151ENST00000569714.6 linkc.484C>T p.Arg162Trp missense_variant Exon 4 of 4 1 NM_174903.6 ENSP00000456566.1 Q2KHN1
RNF151ENST00000321392.4 linkc.481C>T p.Arg161Trp missense_variant Exon 3 of 3 1 ENSP00000325794.3 A0A0C4DFQ4
RNF151ENST00000569210.6 linkc.*244C>T 3_prime_UTR_variant Exon 4 of 4 2 ENSP00000454886.1 H3BNJ8

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152256
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000352
AC:
6
AN:
170518
Hom.:
0
AF XY:
0.0000215
AC XY:
2
AN XY:
93194
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000869
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000304
AC:
43
AN:
1415880
Hom.:
0
Cov.:
32
AF XY:
0.0000286
AC XY:
20
AN XY:
700426
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000263
Gnomad4 ASJ exome
AF:
0.0000394
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000247
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000358
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152256
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000123
AC:
1
ExAC
AF:
0.0000258
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.484C>T (p.R162W) alteration is located in exon 4 (coding exon 4) of the RNF151 gene. This alteration results from a C to T substitution at nucleotide position 484, causing the arginine (R) at amino acid position 162 to be replaced by a tryptophan (W). 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
-0.26
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T;.
Eigen
Uncertain
0.22
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Benign
0.83
T;T
M_CAP
Benign
0.032
D
MetaRNN
Uncertain
0.49
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.81
L;.
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-4.0
D;D
REVEL
Benign
0.13
Sift
Uncertain
0.018
D;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
1.0
D;.
Vest4
0.57
MVP
0.72
MPC
0.51
ClinPred
0.68
D
GERP RS
4.3
Varity_R
0.20
gMVP
0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs372116700; hg19: chr16-2018672; API