3-149846115-T-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2

The NM_183381.3(RNF13):​c.89T>A​(p.Leu30Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000422 in 1,612,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

RNF13
NM_183381.3 missense

Scores

8
11

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B: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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.29483795).
BP6
Variant 3-149846115-T-A is Benign according to our data. Variant chr3-149846115-T-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2374666.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
BS2
High AC in GnomAdExome4 at 67 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RNF13NM_183381.3 linkc.89T>A p.Leu30Gln 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.89T>A p.Leu30Gln missense_variant Exon 2 of 10 1 NM_183381.3 ENSP00000376628.3 O43567-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152184
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
251106
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135708
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000459
AC:
67
AN:
1459856
Hom.:
0
Cov.:
29
AF XY:
0.0000399
AC XY:
29
AN XY:
726420
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000585
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152184
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 09, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.89T>A (p.L30Q) alteration is located in exon 3 (coding exon 1) of the RNF13 gene. This alteration results from a T to A substitution at nucleotide position 89, causing the leucine (L) at amino acid position 30 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Benign:1
Aug 13, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
0.13
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.019
T;T;.;T;.;.;T;T
Eigen
Benign
-0.022
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.93
.;D;D;D;D;D;D;D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.29
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.90
L;L;.;.;.;.;.;.
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-1.0
N;N;N;D;N;N;N;N
REVEL
Benign
0.25
Sift
Uncertain
0.013
D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.045
D;D;D;D;D;D;D;D
Polyphen
0.042
B;B;.;.;.;.;.;.
Vest4
0.97
MVP
0.55
MPC
0.55
ClinPred
0.37
T
GERP RS
5.6
Varity_R
0.34
gMVP
0.69

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: rs145759442; hg19: chr3-149563902; API