13-98176684-C-T

Variant summary

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

The NM_178861.5(RNF113B):​c.553G>A​(p.Ala185Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,148 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 Uncertain significance (★).

Frequency

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

Consequence

RNF113B
NM_178861.5 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.66
Variant links:
Genes affected
RNF113B (HGNC:17267): (ring finger protein 113B) Predicted to enable metal ion binding activity. Predicted to be involved in snoRNA splicing. Predicted to be part of U2-type spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]
FARP1 (HGNC:3591): (FERM, ARH/RhoGEF and pleckstrin domain protein 1) This gene encodes a protein containing a FERM (4.2, exrin, radixin, moesin) domain, a Dbl homology domain, and two pleckstrin homology domains. These domains are found in guanine nucleotide exchange factors and proteins that link the cytoskeleton to the cell membrane. The encoded protein functions in neurons to promote dendritic growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

Genome browser will be placed here

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=0.3263122).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RNF113BNM_178861.5 linkc.553G>A p.Ala185Thr missense_variant Exon 1 of 2 ENST00000267291.7 NP_849192.1 Q8IZP6
FARP1NM_005766.4 linkc.-24+33192C>T intron_variant Intron 1 of 26 ENST00000319562.11 NP_005757.1 Q9Y4F1-1A0A2X0TVY0
FARP1NM_001286839.2 linkc.-24+33907C>T intron_variant Intron 1 of 27 NP_001273768.1 Q9Y4F1C9JME2
FARP1NM_001001715.4 linkc.-24+33192C>T intron_variant Intron 1 of 2 NP_001001715.2 Q9Y4F1-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RNF113BENST00000267291.7 linkc.553G>A p.Ala185Thr missense_variant Exon 1 of 2 1 NM_178861.5 ENSP00000267291.6 Q8IZP6
FARP1ENST00000319562.11 linkc.-24+33192C>T intron_variant Intron 1 of 26 1 NM_005766.4 ENSP00000322926.6 Q9Y4F1-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152148
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:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152148
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 03, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.553G>A (p.A185T) alteration is located in exon 1 (coding exon 1) of the RNF113B gene. This alteration results from a G to A substitution at nucleotide position 553, causing the alanine (A) at amino acid position 185 to be replaced by a threonine (T). 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
0.14
BayesDel_addAF
Benign
-0.082
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T
Eigen
Benign
0.014
Eigen_PC
Benign
-0.11
FATHMM_MKL
Benign
0.69
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.0078
T
MetaRNN
Benign
0.33
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Pathogenic
3.0
M
PrimateAI
Benign
0.41
T
PROVEAN
Uncertain
-2.8
D
REVEL
Benign
0.15
Sift
Uncertain
0.0060
D
Sift4G
Uncertain
0.054
T
Polyphen
0.80
P
Vest4
0.54
MutPred
0.22
Gain of catalytic residue at A185 (P = 0.059);
MVP
0.51
MPC
0.52
ClinPred
0.99
D
GERP RS
1.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.27
gMVP
0.64

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: rs1007297013; hg19: chr13-98828938; API