chr17-79115697-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001350451.2(RBFOX3):c.19C>T(p.Pro7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P7L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000084 ( 5 hom. )

Failed GnomAD Quality Control

Consequence

RBFOX3
NM_001350451.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.94

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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02852559).

BP6

Variant 17-79115697-G-A is Benign according to our data. Variant chr17-79115697-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 460021.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX3	NM_001350451.2 link	c.19C>T	p.Pro7Ser	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.19C>T	p.Pro7Ser	missense_variant	Exon 5 of 15		NM_001350451.2	ENSP00000510395.1		A0A8I5KWJ3

Frequencies

GnomAD3 genomes

AF:

0.000343

AC:

AN:

151710

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000969

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00136

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.000961

GnomAD2 exomes

AF:

0.000117

AC:

AN:

85296

AF XY:

0.0000656

show subpopulations

Gnomad AFR exome

AF:

0.00118

Gnomad AMR exome

AF:

0.0000567

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000283

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000385

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000836

AC:

AN:

634050

Hom.:

Cov.:

AF XY:

0.0000932

AC XY:

AN XY:

332634

show subpopulations

African (AFR)

AF:

0.000713

AC:

AN:

15420

American (AMR)

AF:

0.0000377

AC:

AN:

26508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16046

East Asian (EAS)

AF:

0.000354

AC:

AN:

25388

South Asian (SAS)

AF:

0.00

AC:

AN:

57612

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2368

European-Non Finnish (NFE)

AF:

0.00000462

AC:

AN:

432612

Other (OTH)

AF:

0.000972

AC:

AN:

30870

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.716

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000342

AC:

AN:

151826

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74196

show subpopulations

African (AFR)

AF:

0.000967

AC:

AN:

41384

American (AMR)

AF:

0.0000655

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00136

AC:

AN:

5146

South Asian (SAS)

AF:

0.00

AC:

AN:

4784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67874

Other (OTH)

AF:

0.000951

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.568

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000336

ExAC

AF:

0.000142

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Idiopathic generalized epilepsy

Uncertain:1Benign:1

Oct 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 31, 2018

Fulgent Genetics, Fulgent Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.010

.;.;T;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.91

D;D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.029

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;.;L;L

PhyloP100

1.9

PrimateAI

Uncertain

0.61

Sift4G

Benign

0.54

T;T;T;T

Polyphen

0.0050

.;.;B;.

Vest4

0.11

MutPred

0.11

Gain of phosphorylation at P7 (P = 0.0405);Gain of phosphorylation at P7 (P = 0.0405);Gain of phosphorylation at P7 (P = 0.0405);Gain of phosphorylation at P7 (P = 0.0405);

MVP

0.18

ClinPred

0.030

GERP RS

4.3

PromoterAI

0.036

Neutral

(source)

Varity_R

0.075

gMVP

0.25

Mutation Taster

=86/14

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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