chr2-85596881-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_016494.4(RNF181):​c.277C>T​(p.Pro93Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. P93A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

RNF181
NM_016494.4 missense

Scores

9
7
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.89
Variant links:
Genes affected
RNF181 (HGNC:28037): (ring finger protein 181) RNF181 binds the integrin alpha-IIb (ITGA2B; MIM 607759)/beta-3 (ITGB3; MIM 173470) complex and has E3 ubiquitin ligase activity (Brophy et al., 2008 [PubMed 18331836]).[supplied by OMIM, Dec 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.875

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RNF181NM_016494.4 linkc.277C>T p.Pro93Ser missense_variant Exon 3 of 5 ENST00000306368.9 NP_057578.1 Q9P0P0
RNF181XM_005264359.5 linkc.218-72C>T intron_variant Intron 2 of 3 XP_005264416.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RNF181ENST00000306368.9 linkc.277C>T p.Pro93Ser missense_variant Exon 3 of 5 1 NM_016494.4 ENSP00000306906.4 Q9P0P0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.88
BayesDel_addAF
Pathogenic
0.34
D
BayesDel_noAF
Pathogenic
0.25
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.11
T;T
Eigen
Pathogenic
0.86
Eigen_PC
Pathogenic
0.85
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.97
D;D
M_CAP
Benign
0.077
D
MetaRNN
Pathogenic
0.88
D;D
MetaSVM
Uncertain
0.12
D
MutationAssessor
Uncertain
2.4
.;M
PrimateAI
Uncertain
0.60
T
PROVEAN
Pathogenic
-7.6
D;D
REVEL
Pathogenic
0.66
Sift
Uncertain
0.0090
D;D
Sift4G
Uncertain
0.0060
D;D
Polyphen
1.0
.;D
Vest4
0.77
MutPred
0.71
Loss of catalytic residue at P93 (P = 0.0245);Loss of catalytic residue at P93 (P = 0.0245);
MVP
0.80
MPC
0.83
ClinPred
1.0
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.71
gMVP
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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: rs1369745792; hg19: chr2-85824004; API