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17-79094472-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001350451.2(RBFOX3):c.1056G>A(p.Ala352=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,476,142 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

RBFOX3
NM_001350451.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.401
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-79094472-C-T is Benign according to our data. Variant chr17-79094472-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 529528.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.401 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAdExome at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RBFOX3NM_001350451.2 linkuse as main transcriptc.1056G>A p.Ala352= synonymous_variant 14/15 ENST00000693108.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RBFOX3ENST00000693108.1 linkuse as main transcriptc.1056G>A p.Ala352= synonymous_variant 14/15 NM_001350451.2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000264
AC:
4
AN:
151508
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000658
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:
0.0000295
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000659
AC:
6
AN:
91080
Hom.:
0
AF XY:
0.000100
AC XY:
5
AN XY:
49858
show subpopulations
Gnomad AFR exome
AF:
0.000306
Gnomad AMR exome
AF:
0.0000843
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000540
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000219
AC:
29
AN:
1324634
Hom.:
0
Cov.:
31
AF XY:
0.0000261
AC XY:
17
AN XY:
650778
show subpopulations
Gnomad4 AFR exome
AF:
0.0000756
Gnomad4 AMR exome
AF:
0.0000869
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000423
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000201
Gnomad4 OTH exome
AF:
0.0000183
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000264
AC:
4
AN:
151508
Hom.:
0
Cov.:
30
AF XY:
0.0000135
AC XY:
1
AN XY:
73934
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.0000658
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000295
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000865
Hom.:
0
Bravo
AF:
0.0000642

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Idiopathic generalized epilepsy Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 15, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
Cadd
Benign
7.6
Dann
Benign
0.83

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: rs1228682560; hg19: chr17-77090554; API