1-51270109-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014372.5(RNF11):​c.277G>A​(p.Glu93Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RNF11
NM_014372.5 missense

Scores

3
3
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.50
Variant links:
Genes affected
RNF11 (HGNC:10056): (ring finger protein 11) The protein encoded by this gene contains a RING-H2 finger motif, which is known to be important for protein-protein interactions. The expression of this gene has been shown to be induced by mutant RET proteins (MEN2A/MEN2B). The germline mutations in RET gene are known to be responsible for the development of multiple endocrine neoplasia (MEN). [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3217882).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNF11NM_014372.5 linkuse as main transcriptc.277G>A p.Glu93Lys missense_variant 2/3 ENST00000242719.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF11ENST00000242719.4 linkuse as main transcriptc.277G>A p.Glu93Lys missense_variant 2/31 NM_014372.5 P1
RNF11ENST00000486691.1 linkuse as main transcriptn.192G>A non_coding_transcript_exon_variant 1/22
RNF11ENST00000494873.1 linkuse as main transcriptn.542-1042G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
6.95e-7
AC:
1
AN:
1438616
Hom.:
0
Cov.:
29
AF XY:
0.00000140
AC XY:
1
AN XY:
715038
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:
0.0000123
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.73
BayesDel_addAF
Benign
-0.053
T
BayesDel_noAF
Benign
-0.31
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.067
T
Eigen
Benign
-0.036
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.32
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
0.36
N
REVEL
Benign
0.21
Sift
Benign
0.61
T
Sift4G
Benign
0.64
T
Polyphen
0.0020
B
Vest4
0.64
MutPred
0.37
Loss of ubiquitination at K94 (P = 0.0193);
MVP
0.40
MPC
1.0
ClinPred
0.97
D
GERP RS
5.9
Varity_R
0.29
gMVP
0.68

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: rs1220574608; hg19: chr1-51735781; API