1-228493225-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001010858.3(RNF187):​c.656C>T​(p.Ser219Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,551,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

RNF187
NM_001010858.3 missense

Scores

1
1
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.637
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.016852558).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RNF187NM_001010858.3 linkc.656C>T p.Ser219Leu missense_variant Exon 3 of 4 ENST00000305943.9 NP_001010858.2 Q5TA31

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RNF187ENST00000305943.9 linkc.656C>T p.Ser219Leu missense_variant Exon 3 of 4 1 NM_001010858.3 ENSP00000306396.9 Q5TA31A0A1X7SBW3
RNF187ENST00000482739.3 linkn.534C>T non_coding_transcript_exon_variant Exon 3 of 4 5

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000579
AC:
9
AN:
155546
Hom.:
0
AF XY:
0.0000606
AC XY:
5
AN XY:
82498
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000162
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000918
Gnomad SAS exome
AF:
0.0000878
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000333
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000150
AC:
21
AN:
1399156
Hom.:
0
Cov.:
31
AF XY:
0.0000203
AC XY:
14
AN XY:
690096
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000840
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000560
Gnomad4 SAS exome
AF:
0.000114
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000463
Gnomad4 OTH exome
AF:
0.0000345
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152330
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.0000367
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 03, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.656C>T (p.S219L) alteration is located in exon 3 (coding exon 3) of the RNF187 gene. This alteration results from a C to T substitution at nucleotide position 656, causing the serine (S) at amino acid position 219 to be replaced by a leucine (L). 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
0.21
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
17
DANN
Benign
0.86
DEOGEN2
Benign
0.035
.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.046
N
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.017
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
.;N
PrimateAI
Uncertain
0.76
T
REVEL
Benign
0.037
Sift4G
Pathogenic
0.0
D;.
Polyphen
0.0020
.;B
Vest4
0.13
MutPred
0.41
Loss of phosphorylation at S219 (P = 0.0367);Loss of phosphorylation at S219 (P = 0.0367);
MVP
0.040
ClinPred
0.031
T
GERP RS
0.83
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.081
gMVP
0.83

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: rs558425555; hg19: chr1-228680926; COSMIC: COSV59960064; API