1-77956687-CGT-AGC

Variant names:

• chr1-77956687-CGT-AGC
• NM_003902.5:c.1588_1590delACGinsGCT
• FUBP1 p.Thr530Ala

Variant summary

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

The NM_003902.5(FUBP1):​c.1588_1590delACGinsGCT​(p.Thr530Ala) 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: FUBP1 NM_003902.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.36
• Publications: 0 publications found

Genes affected

FUBP1 (HGNC:4004): (far upstream element binding protein 1) The protein encoded by this gene is a single stranded DNA-binding protein that binds to multiple DNA elements, including the far upstream element (FUSE) located upstream of c-myc. Binding to FUSE occurs on the non-coding strand, and is important to the regulation of c-myc in undifferentiated cells. This protein contains three domains, an amphipathic helix N-terminal domain, a DNA-binding central domain, and a C-terminal transactivation domain that contains three tyrosine-rich motifs. The N-terminal domain is thought to repress the activity of the C-terminal domain. This protein is also thought to bind RNA, and contains 3'-5' helicase activity with in vitro activity on both DNA-DNA and RNA-RNA duplexes. Aberrant expression of this gene has been found in malignant tissues, and this gene is important to neural system and lung development. Binding of this protein to viral RNA is thought to play a role in several viral diseases, including hepatitis C and hand, foot and mouth disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

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_003902.5. 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
	FUBP1	NM_003902.5	MANE Select	c.1588_1590delACGinsGCT	p.Thr530Ala	missense	N/A	NP_003893.2
	FUBP1	NM_001410804.1		c.1648_1650delACGinsGCT	p.Thr550Ala	missense	N/A	NP_001397733.1	C9JSZ1
	FUBP1	NM_001376056.1		c.1585_1587delACGinsGCT	p.Thr529Ala	missense	N/A	NP_001362985.1	A0A994J3Q8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUBP1	ENST00000370768.7	TSL:1 MANE Select	c.1588_1590delACGinsGCT	p.Thr530Ala	missense	N/A	ENSP00000359804.2	Q96AE4-1
	FUBP1	ENST00000294623.8	TSL:1	n.1585_1587delACGinsGCT		non_coding_transcript_exon	Exon 17 of 21	ENSP00000294623.4	Q96AE4-2
	FUBP1	ENST00000421641.2	TSL:5	c.1648_1650delACGinsGCT	p.Thr550Ala	missense	N/A	ENSP00000402630.2	C9JSZ1

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		9.4

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: chr1-78422372;