rs1555812114

Variant names:

• chr16-7709100-C-A
• NM_018723.4:c.1040C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-7709100-C-A
• chr16-7709100-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018723.4(RBFOX1):​c.1040C>A​(p.Ala347Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,228 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RBFOX1 NM_018723.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.44

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.1040C>A	p.Ala347Asp	missense_variant	Exon 15 of 16	ENST00000550418.6	NP_061193.2
RBFOX1	NM_145893.3	c.1156C>A	p.Leu386Ile	missense_variant	Exon 13 of 14	ENST00000355637.9	NP_665900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6	c.1040C>A	p.Ala347Asp	missense_variant	Exon 15 of 16	1	NM_018723.4	ENSP00000450031.1
RBFOX1	ENST00000355637.9	c.1156C>A	p.Leu386Ile	missense_variant	Exon 13 of 14	1	NM_145893.3	ENSP00000347855.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461228 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726890

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	.;T;T;T;.;.;.;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D;.;D;D;D;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.53	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.0	.;N;.;N;.;.;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.0	N;N;N;N;N;N;N;.
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D;D;D;D;D;D;D;.
Sift4G	Uncertain	0.017	D;D;D;D;D;D;D;D
Polyphen		0.57	P;B;D;B;P;P;.;.
Vest4		0.89
MutPred		0.39		.;.;Gain of catalytic residue at A390 (P = 0.0676);.;.;.;.;.;
MVP		0.42
MPC		1.9
ClinPred		0.73	D
GERP RS		5.7
Varity_R		0.48
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-7759102;