chr13-98176623-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_178861.5(RNF113B):​c.614G>A​(p.Cys205Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000328 in 1,614,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

RNF113B
NM_178861.5 missense

Scores

10
7
2

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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RNF113BNM_178861.5 linkc.614G>A p.Cys205Tyr missense_variant Exon 1 of 2 ENST00000267291.7 NP_849192.1 Q8IZP6
FARP1NM_005766.4 linkc.-24+33131C>T intron_variant Intron 1 of 26 ENST00000319562.11 NP_005757.1 Q9Y4F1-1A0A2X0TVY0
FARP1NM_001286839.2 linkc.-24+33846C>T intron_variant Intron 1 of 27 NP_001273768.1 Q9Y4F1C9JME2
FARP1NM_001001715.4 linkc.-24+33131C>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.614G>A p.Cys205Tyr missense_variant Exon 1 of 2 1 NM_178861.5 ENSP00000267291.6 Q8IZP6
FARP1ENST00000319562.11 linkc.-24+33131C>T intron_variant Intron 1 of 26 1 NM_005766.4 ENSP00000322926.6 Q9Y4F1-1

Frequencies

GnomAD3 genomes
AF:
0.000151
AC:
23
AN:
152232
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000555
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000756
AC:
19
AN:
251440
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.00117
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000205
AC:
30
AN:
1461894
Hom.:
0
Cov.:
32
AF XY:
0.0000206
AC XY:
15
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.000836
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:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.000151
AC:
23
AN:
152350
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.000553
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000476
Hom.:
0
Bravo
AF:
0.000185
ESP6500AA
AF:
0.00182
AC:
8
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000115
AC:
14

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 26, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.614G>A (p.C205Y) 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 614, causing the cysteine (C) at amino acid position 205 to be replaced by a tyrosine (Y). 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
Pathogenic
0.89
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Pathogenic
0.33
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.42
T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Benign
0.68
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Uncertain
0.17
D
MetaRNN
Pathogenic
0.82
D
MetaSVM
Pathogenic
0.92
D
MutationAssessor
Pathogenic
3.9
H
PrimateAI
Uncertain
0.51
T
PROVEAN
Pathogenic
-11
D
REVEL
Pathogenic
0.72
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.83
MVP
1.0
MPC
1.8
ClinPred
0.98
D
GERP RS
1.2
Varity_R
0.92
gMVP
0.96

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: rs150082041; hg19: chr13-98828877; API