NM_001350451.2:c.1053G>A

Variant names:

• chr17-79094475-C-T
• rs1305432887
• NM_001350451.2:c.1053G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001350451.2(RBFOX3):​c.1053G>A​(p.Ala351Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,301,158 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: not found (cov: 30)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: RBFOX3 NM_001350451.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.43
• 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, NO_KNOWN Submitted by: ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 17-79094475-C-T is Benign according to our data. Variant chr17-79094475-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 999470.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.43 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 29 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX3	NM_001350451.2	MANE Select	c.1053G>A	p.Ala351Ala	synonymous	Exon 14 of 15	NP_001337380.1	A0A8I5KWJ3
	RBFOX3	NM_001385804.1		c.1053G>A	p.Ala351Ala	synonymous	Exon 14 of 15	NP_001372733.1
	RBFOX3	NM_001385805.1		c.1053G>A	p.Ala351Ala	synonymous	Exon 15 of 16	NP_001372734.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX3	ENST00000693108.1	MANE Select	c.1053G>A	p.Ala351Ala	synonymous	Exon 14 of 15	ENSP00000510395.1	A0A8I5KWJ3
	RBFOX3	ENST00000857749.1		c.1149G>A	p.Ala383Ala	synonymous	Exon 14 of 15	ENSP00000527808.1
	RBFOX3	ENST00000583458.5	TSL:5	c.1050G>A	p.Ala350Ala	synonymous	Exon 13 of 14	ENSP00000464186.1	J3QRF4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.0000430 AC: 4 AN: 92936 AF XY: 0.0000591

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000820

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000223 AC: 29 AN: 1301158 Hom.: 0 Cov.: 31 AF XY: 0.0000298 AC XY: 19 AN XY: 638596

African (AFR) AF: 0.000117 AC: 3 AN: 25696

American (AMR) AF: 0.00 AC: 0 AN: 22356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21906

East Asian (EAS) AF: 0.000369 AC: 10 AN: 27110

South Asian (SAS) AF: 0.000113 AC: 8 AN: 70812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5260

European-Non Finnish (NFE) AF: 0.00000679 AC: 7 AN: 1031412

Other (OTH) AF: 0.0000188 AC: 1 AN: 53182

GnomAD4 genome Cov.: 30

Alfa AF: 0.0000577 Hom.: 0

ClinVar

ClinVar submissions

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	-0.51
CADD	Benign	7.2
DANN	Benign	0.76
PhyloP100		-2.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1305432887; hg19: chr17-77090557;