3-149846031-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_183381.3(RNF13):​c.5T>A​(p.Leu2Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RNF13
NM_183381.3 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.19
Variant links:
Genes affected
RNF13 (HGNC:10057): (ring finger protein 13) The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. The specific function of this gene has not yet been determined. Alternatively spliced transcript variants that encode the same protein have been reported. A pseudogene, which is also located on chromosome 3, has been defined for this gene. [provided by RefSeq, Jul 2008]
ANKUB1 (HGNC:29642): (ankyrin repeat and ubiquitin domain containing 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RNF13NM_183381.3 linkc.5T>A p.Leu2Gln missense_variant Exon 2 of 10 ENST00000392894.8 NP_899237.1 O43567-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RNF13ENST00000392894.8 linkc.5T>A p.Leu2Gln missense_variant Exon 2 of 10 1 NM_183381.3 ENSP00000376628.3 O43567-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Jun 02, 2024
GeneDx
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.34
BayesDel_addAF
Pathogenic
0.30
D
BayesDel_noAF
Pathogenic
0.19
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.018
T;T;.;T;.;.;T;T
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.88
.;D;D;D;D;D;D;D
M_CAP
Benign
0.032
D
MetaRNN
Uncertain
0.66
D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.67
T
MutationAssessor
Benign
0.69
N;N;.;.;.;.;.;.
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-0.77
N;N;N;D;N;N;N;N
REVEL
Uncertain
0.29
Sift
Pathogenic
0.0
D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.0080
D;D;D;D;D;D;D;D
Polyphen
1.0
D;D;.;.;.;.;.;.
Vest4
0.85
MutPred
0.41
Gain of disorder (P = 0.026);Gain of disorder (P = 0.026);Gain of disorder (P = 0.026);Gain of disorder (P = 0.026);Gain of disorder (P = 0.026);Gain of disorder (P = 0.026);Gain of disorder (P = 0.026);Gain of disorder (P = 0.026);
MVP
0.84
MPC
0.74
ClinPred
0.96
D
GERP RS
5.6
Varity_R
0.51
gMVP
0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-149563818; API