chr17-79115613-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001350451.2(RBFOX3):c.103G>A(p.Gly35Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00043 in 1,285,514 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 0.00052 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

RBFOX3
NM_001350451.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 7.13

Publications

1 publications found

Variant links:

Genes affected

RBFOX3 (HGNC:27097): (RNA binding fox-1 homolog 3) This gene encodes a member of the RNA-binding FOX protein family which is involved in the regulation of alternative splicing of pre-mRNA. The protein has an N-terminal proline-rich region, an RNA recognition motif (RRM) domain, and a C-terminal alanine-rich region. This gene produces the neuronal nuclei (NeuN) antigen that has been widely used as a marker for post-mitotic neurons. This gene has its highest expression in the central nervous system and plays a prominent role in neural tissue development and regulation of adult brain function. Mutations in this gene have been associated with numerous neurological disorders. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2017]

RBFOX3 Gene-Disease associations (from GenCC):

epilepsy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

RBFOX3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0076612234).

BP6

Variant 17-79115613-C-T is Benign according to our data. Variant chr17-79115613-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 460020.We mark this variant Likely_benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].

BS2

High AC in GnomAd4 at 67 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX3	NM_001350451.2 link	c.103G>A	p.Gly35Ser	missense_variant	Exon 5 of 15	ENST00000693108.1	NP_001337380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX3	ENST00000693108.1 link	c.103G>A	p.Gly35Ser	missense_variant	Exon 5 of 15		NM_001350451.2	ENSP00000510395.1		A0A8I5KWJ3

Frequencies

GnomAD3 genomes

AF:

0.000521

AC:

AN:

128512

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000118

Gnomad AMI

AF:

0.0390

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00181

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000328

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000297

AC:

AN:

60614

AF XY:

0.000393

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000360

Gnomad ASJ exome

AF:

0.000995

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000448

Gnomad OTH exome

AF:

0.000576

GnomAD4 exome

AF:

0.000420

AC:

486

AN:

1157002

Hom.:

Cov.:

AF XY:

0.000432

AC XY:

242

AN XY:

560240

show subpopulations

African (AFR)

AF:

0.000300

AC:

AN:

23372

American (AMR)

AF:

0.000399

AC:

AN:

17564

Ashkenazi Jewish (ASJ)

AF:

0.00327

AC:

AN:

14356

East Asian (EAS)

AF:

0.0000969

AC:

AN:

20632

South Asian (SAS)

AF:

0.0000165

AC:

AN:

60666

European-Finnish (FIN)

AF:

0.000154

AC:

AN:

25998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4522

European-Non Finnish (NFE)

AF:

0.000430

AC:

406

AN:

944940

Other (OTH)

AF:

0.000267

AC:

AN:

44952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000521

AC:

AN:

128512

Hom.:

Cov.:

AF XY:

0.000595

AC XY:

AN XY:

60484

show subpopulations

African (AFR)

AF:

0.000118

AC:

AN:

33864

American (AMR)

AF:

0.000196

AC:

AN:

10190

Ashkenazi Jewish (ASJ)

AF:

0.00181

AC:

AN:

3324

East Asian (EAS)

AF:

0.00

AC:

AN:

3962

South Asian (SAS)

AF:

0.00

AC:

AN:

3844

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6428

Middle Eastern (MID)

AF:

0.00

AC:

AN:

202

European-Non Finnish (NFE)

AF:

0.000328

AC:

AN:

64064

Other (OTH)

AF:

0.00

AC:

AN:

1762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000516

Hom.:

Bravo

AF:

0.000567

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.0000997

AC:

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

Dec 06, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.103G>A (p.G35S) alteration is located in exon 4 (coding exon 1) of the RBFOX3 gene. This alteration results from a G to A substitution at nucleotide position 103, causing the glycine (G) at amino acid position 35 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Idiopathic generalized epilepsy

Benign:1

Jan 05, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

.;.;T;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D;D;D

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.0077

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.3

.;.;M;M

PhyloP100

7.1

PrimateAI

Pathogenic

0.85

Sift4G

Benign

0.094

T;T;T;T

Polyphen

1.0

.;.;D;.

Vest4

0.42

MVP

0.35

ClinPred

0.37

GERP RS

3.0

PromoterAI

0.0049

Neutral

(source)

Varity_R

0.28

gMVP

0.29

Mutation Taster

=77/23

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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chr17-79115613-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over