1-228487624-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001010858.3(RNF187):​c.136C>G​(p.Pro46Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000326 in 1,227,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

RNF187
NM_001010858.3 missense

Scores

2
1
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0150
Variant links:
Genes affected
RNF187 (HGNC:27146): (ring finger protein 187) Enables ubiquitin-protein transferase activity. Involved in positive regulation of transcription, DNA-templated; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein ubiquitination. Located in cytosol and nucleoplasm. [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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18385762).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RNF187NM_001010858.3 linkc.136C>G p.Pro46Ala missense_variant Exon 1 of 4 ENST00000305943.9 NP_001010858.2 Q5TA31

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RNF187ENST00000305943.9 linkc.136C>G p.Pro46Ala missense_variant Exon 1 of 4 1 NM_001010858.3 ENSP00000306396.9 Q5TA31A0A1X7SBW3

Frequencies

GnomAD3 genomes
AF:
0.00000672
AC:
1
AN:
148770
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000668
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000278
AC:
3
AN:
1078616
Hom.:
0
Cov.:
30
AF XY:
0.00000382
AC XY:
2
AN XY:
523800
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:
0.0000506
Gnomad4 NFE exome
AF:
0.00000111
Gnomad4 OTH exome
AF:
0.0000251
GnomAD4 genome
AF:
0.00000672
AC:
1
AN:
148878
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
72620
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000667
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 08, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.136C>G (p.P46A) alteration is located in exon 1 (coding exon 1) of the RNF187 gene. This alteration results from a C to G substitution at nucleotide position 136, causing the proline (P) at amino acid position 46 to be replaced by an alanine (A). 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
0.16
BayesDel_addAF
Benign
-0.00082
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
22
DANN
Benign
0.91
DEOGEN2
Uncertain
0.44
.;T
FATHMM_MKL
Benign
0.033
N
MetaRNN
Benign
0.18
T;T
MutationAssessor
Benign
1.3
.;L
PrimateAI
Pathogenic
0.81
D
Sift4G
Pathogenic
0.0
D;.
Polyphen
0.099
.;B
Vest4
0.13
MVP
0.67
GERP RS
-0.39
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.083
gMVP
0.15

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: rs1658865512; hg19: chr1-228675325; API