rs972548690

Variant names:

• chr17-79094526-G-A
• rs972548690
• NM_001350451.2:c.1002C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-79094526-G-A
• chr17-79094526-G-T

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.1002C>T​(p.Tyr334Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000324 in 1,143,614 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 0.000035 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: RBFOX3 NM_001350451.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.169
• Publications: 1 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 17-79094526-G-A is Benign according to our data. Variant chr17-79094526-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 700707.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.169 with no splicing effect.
• BS2: High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX3	NM_001350451.2	c.1002C>T	p.Tyr334Tyr	synonymous_variant	Exon 14 of 15	ENST00000693108.1	NP_001337380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX3	ENST00000693108.1	c.1002C>T	p.Tyr334Tyr	synonymous_variant	Exon 14 of 15		NM_001350451.2	ENSP00000510395.1

Frequencies

GnomAD3 genomes AF: 0.0000352 AC: 5 AN: 141898 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000770

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000307

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000172 AC: 1 AN: 58164 AF XY: 0.00

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: 0.00

Gnomad NFE exome AF: 0.0000368

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000319 AC: 32 AN: 1001716 Hom.: 0 Cov.: 29 AF XY: 0.0000247 AC XY: 12 AN XY: 485258

African (AFR) AF: 0.0000592 AC: 1 AN: 16900

American (AMR) AF: 0.00 AC: 0 AN: 7390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12774

East Asian (EAS) AF: 0.00 AC: 0 AN: 6684

South Asian (SAS) AF: 0.00 AC: 0 AN: 58730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3296

European-Non Finnish (NFE) AF: 0.0000370 AC: 31 AN: 837566

Other (OTH) AF: 0.00 AC: 0 AN: 36000

GnomAD4 genome AF: 0.0000352 AC: 5 AN: 141898 Hom.: 0 Cov.: 29 AF XY: 0.0000437 AC XY: 3 AN XY: 68702

African (AFR) AF: 0.0000770 AC: 3 AN: 38952

American (AMR) AF: 0.00 AC: 0 AN: 14258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3334

East Asian (EAS) AF: 0.00 AC: 0 AN: 4098

South Asian (SAS) AF: 0.00 AC: 0 AN: 4026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.0000307 AC: 2 AN: 65160

Other (OTH) AF: 0.00 AC: 0 AN: 1976

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000264

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Idiopathic generalized epilepsy Benign:1

Nov 07, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.3
DANN	Benign	0.70
PhyloP100		-0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs972548690; hg19: chr17-77090608; COSMIC: COSV70555882;