Genetic Variant NM_178861.5:c.536C>A (chr13-98176701-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_178861.5(RNF113B):c.536C>A(p.Ala179Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A179G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

RNF113B
NM_178861.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.34

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178861.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF113B	NM_178861.5	MANE Select	c.536C>A	p.Ala179Glu	missense	Exon 1 of 2	NP_849192.1	Q8IZP6
FARP1	NM_005766.4	MANE Select	c.-24+33209G>T		intron	N/A	NP_005757.1	A0A2X0TVY0
FARP1	NM_001286839.2		c.-24+33924G>T		intron	N/A	NP_001273768.1	C9JME2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF113B	ENST00000267291.7	TSL:1 MANE Select	c.536C>A	p.Ala179Glu	missense	Exon 1 of 2	ENSP00000267291.6	Q8IZP6
FARP1	ENST00000319562.11	TSL:1 MANE Select	c.-24+33209G>T		intron	N/A	ENSP00000322926.6	Q9Y4F1-1
FARP1	ENST00000595437.5	TSL:1	c.-24+33924G>T		intron	N/A	ENSP00000471242.1	C9JME2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251364

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.037

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.58

MutationAssessor

Pathogenic

3.2

PhyloP100

5.3

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.23

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.61

MutPred

0.31

Loss of MoRF binding (P = 0.0145)

MVP

0.77

MPC

1.5

ClinPred

0.99

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.64

gMVP

0.87

Mutation Taster

=76/24

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over