6-13977547-C-A

Variant summary

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

The NM_152737.4(RNF182):​c.428C>A​(p.Ser143Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

RNF182
NM_152737.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06
Variant links:
Genes affected
RNF182 (HGNC:28522): (ring finger protein 182) Enables ubiquitin-protein transferase activity. Involved in protein ubiquitination. Located in cytoplasm. [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=0.13541934).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RNF182NM_152737.4 linkc.428C>A p.Ser143Tyr missense_variant Exon 3 of 3 ENST00000488300.6 NP_689950.1 Q8N6D2A0A024QZW5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RNF182ENST00000488300.6 linkc.428C>A p.Ser143Tyr missense_variant Exon 3 of 3 1 NM_152737.4 ENSP00000420465.1 Q8N6D2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000319
AC:
8
AN:
251156
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135722
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000435
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461874
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.428C>A (p.S143Y) alteration is located in exon 4 (coding exon 1) of the RNF182 gene. This alteration results from a C to A substitution at nucleotide position 428, causing the serine (S) at amino acid position 143 to be replaced by a tyrosine (Y). 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
0.15
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
20
DANN
Benign
0.96
DEOGEN2
Benign
0.19
T;T;T;.;T
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.26
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.84
.;.;.;T;T
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.14
T;T;T;T;T
MetaSVM
Benign
-0.70
T
MutationAssessor
Benign
1.7
L;L;L;.;L
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-2.8
D;D;D;D;D
REVEL
Benign
0.13
Sift
Uncertain
0.0070
D;D;D;D;D
Sift4G
Benign
0.086
T;T;T;T;T
Polyphen
0.0010
B;B;B;.;B
Vest4
0.13
MutPred
0.20
Loss of disorder (P = 0.0253);Loss of disorder (P = 0.0253);Loss of disorder (P = 0.0253);Loss of disorder (P = 0.0253);Loss of disorder (P = 0.0253);
MVP
0.85
MPC
0.19
ClinPred
0.16
T
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.22
gMVP
0.51

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: rs749580920; hg19: chr6-13977778; API