16-7518270-GAG-AAA

Variant names:

• chr16-7518270-GAG-AAA
• NM_018723.4:c.151_153delGAGinsAAA
• RBFOX1 p.Glu51Lys

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_018723.4(RBFOX1):​c.151_153delGAGinsAAA​(p.Glu51Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBFOX1 NM_018723.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.17
• Publications: 0 publications found

Genes affected

RBFOX1 (HGNC:18222): (RNA binding fox-1 homolog 1) The Fox-1 family of RNA-binding proteins is evolutionarily conserved, and regulates tissue-specific alternative splicing in metazoa. Fox-1 recognizes a (U)GCAUG stretch in regulated exons or in flanking introns. The protein binds to the C-terminus of ataxin-2 and may contribute to the restricted pathology of spinocerebellar ataxia type 2 (SCA2). Ataxin-2 is the product of the SCA2 gene which causes familial neurodegenerative diseases. Fox-1 and ataxin-2 are both localized in the trans-Golgi network. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

RBFOX1 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• autism susceptibility 1

  Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018723.4. 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
	RBFOX1	NM_018723.4	MANE Select	c.151_153delGAGinsAAA	p.Glu51Lys	missense	N/A	NP_061193.2
	RBFOX1	NM_145893.3	MANE Plus Clinical	c.211_213delGAGinsAAA	p.Glu71Lys	missense	N/A	NP_665900.1	Q9NWB1-5
	RBFOX1	NM_001415887.1		c.748_750delGAGinsAAA	p.Glu250Lys	missense	N/A	NP_001402816.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	ENST00000550418.6	TSL:1 MANE Select	c.151_153delGAGinsAAA	p.Glu51Lys	missense	N/A	ENSP00000450031.1	Q9NWB1-1
	RBFOX1	ENST00000355637.9	TSL:1 MANE Plus Clinical	c.211_213delGAGinsAAA	p.Glu71Lys	missense	N/A	ENSP00000347855.4	Q9NWB1-5
	RBFOX1	ENST00000311745.9	TSL:1	c.211_213delGAGinsAAA	p.Glu71Lys	missense	N/A	ENSP00000309117.5	Q9NWB1-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-7568272;