chr13-98176986-T-G

Position:

chr13-98176986-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178861.5(RNF113B):c.251A>C(p.Glu84Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000275 in 1,598,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

RNF113B
NM_178861.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.677

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]

RNF113B links:

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]

FARP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07036066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RNF113B	NM_178861.5 linkuse as main transcript	c.251A>C	p.Glu84Ala	missense_variant	1/2	ENST00000267291.7
FARP1	NM_005766.4 linkuse as main transcript	c.-24+33494T>G		intron_variant		ENST00000319562.11
FARP1	NM_001001715.4 linkuse as main transcript	c.-24+33494T>G		intron_variant
FARP1	NM_001286839.2 linkuse as main transcript	c.-24+34209T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF113B	ENST00000267291.7 linkuse as main transcript	c.251A>C	p.Glu84Ala	missense_variant	1/2	1	NM_178861.5	P1
FARP1	ENST00000319562.11 linkuse as main transcript	c.-24+33494T>G		intron_variant		1	NM_005766.4	P1	Q9Y4F1-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151814

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000770

AC:

AN:

233896

Hom.:

AF XY:

0.0000469

AC XY:

AN XY:

127964

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000922

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000290

AC:

AN:

1446982

Hom.:

Cov.:

AF XY:

0.0000236

AC XY:

AN XY:

720208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151814

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74120

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

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

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000414

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2023

The c.251A>C (p.E84A) alteration is located in exon 1 (coding exon 1) of the RNF113B gene. This alteration results from a A to C substitution at nucleotide position 251, causing the glutamic acid (E) at amino acid position 84 to be replaced by an alanine (A). 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

0.066

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.061

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.42

M_CAP

Benign

0.0022

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.2

REVEL

Benign

0.040

Sift

Benign

0.096

Sift4G

Benign

0.26

Polyphen

0.38

Vest4

0.15

MVP

0.33

MPC

0.51

ClinPred

0.034

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.064

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over