16-7630634-G-T

Variant names:

• chr16-7630634-G-T
• NM_018723.4:c.708G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018723.4(RBFOX1):​c.708G>T​(p.Glu236Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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: 3.33

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14102733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.708G>T	p.Glu236Asp	missense_variant	Exon 11 of 16	ENST00000550418.6	NP_061193.2
RBFOX1	NM_145893.3	c.768G>T	p.Glu256Asp	missense_variant	Exon 8 of 14	ENST00000355637.9	NP_665900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6	c.708G>T	p.Glu236Asp	missense_variant	Exon 11 of 16	1	NM_018723.4	ENSP00000450031.1
RBFOX1	ENST00000355637.9	c.768G>T	p.Glu256Asp	missense_variant	Exon 8 of 14	1	NM_145893.3	ENSP00000347855.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

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	Benign	0.082
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	.;.;T;.;T;.;.;.;T;.;.;.;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.017
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.97	D;D;.;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;.;N;.;.;.;.;.;N;.;.;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.61	.;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.20	.;T;T;D;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.60	.;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0090, 0.0030, 0.091, 0.77, 0.038, 0.082, 0.23	.;.;B;B;B;P;.;.;B;B;B;B;.
Vest4		0.66, 0.74, 0.72, 0.70, 0.69, 0.66, 0.72, 0.72, 0.68, 0.73
MutPred		0.50		.;.;.;Loss of glycosylation at S281 (P = 0.1292);Loss of glycosylation at S281 (P = 0.1292);.;.;.;.;.;.;.;.;
MVP		0.66
MPC		0.81
ClinPred		0.46	T
GERP RS		3.8
Varity_R		0.095
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: 49

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: chr16-7680636;