NM_001350451.2:c.30C>T

Variant names:

• chr17-79115686-G-A
• rs1555694660
• NM_001350451.2:c.30C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001350451.2(RBFOX3):​c.30C>T​(p.Tyr10Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RBFOX3 NM_001350451.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.870
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 17-79115686-G-A is Benign according to our data. Variant chr17-79115686-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 529530.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.87 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350451.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX3	NM_001350451.2	MANE Select	c.30C>T	p.Tyr10Tyr	synonymous	Exon 5 of 15	NP_001337380.1
	RBFOX3	NM_001385804.1		c.30C>T	p.Tyr10Tyr	synonymous	Exon 5 of 15	NP_001372733.1
	RBFOX3	NM_001385805.1		c.30C>T	p.Tyr10Tyr	synonymous	Exon 6 of 16	NP_001372734.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX3	ENST00000693108.1	MANE Select	c.30C>T	p.Tyr10Tyr	synonymous	Exon 5 of 15	ENSP00000510395.1
	RBFOX3	ENST00000583458.5	TSL:5	c.30C>T	p.Tyr10Tyr	synonymous	Exon 4 of 14	ENSP00000464186.1
	RBFOX3	ENST00000582043.5	TSL:5	c.30C>T	p.Tyr10Tyr	synonymous	Exon 2 of 11	ENSP00000463964.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 308506 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 167940

African (AFR) AF: 0.00 AC: 0 AN: 7202

American (AMR) AF: 0.00 AC: 0 AN: 15440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8476

East Asian (EAS) AF: 0.00 AC: 0 AN: 14156

South Asian (SAS) AF: 0.00 AC: 0 AN: 44380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 185544

Other (OTH) AF: 0.00 AC: 0 AN: 15526

GnomAD4 genome Cov.: 25

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Idiopathic generalized epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.2
DANN	Benign	0.73
PhyloP100		0.87
PromoterAI		-0.021	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1555694660; hg19: chr17-77111768;