10-101354217-CTC-GTA

Variant names:

• chr10-101354217-CTC-GTA
• NM_033637.4:c.37_39delCTCinsGTA
• BTRC p.Leu13Val

Variant summary

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

The NM_033637.4(BTRC):​c.37_39delCTCinsGTA​(p.Leu13Val) variant causes a missense change. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. L13I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BTRC NM_033637.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.23
• Publications: 0 publications found

Genes affected

BTRC (HGNC:1144): (beta-transducin repeat containing E3 ubiquitin protein ligase) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbws class; in addition to an F-box, this protein contains multiple WD-40 repeats. The encoded protein mediates degradation of CD4 via its interaction with HIV-1 Vpu. It has also been shown to ubiquitinate phosphorylated NFKBIA (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), targeting it for degradation and thus activating nuclear factor kappa-B. Alternatively spliced transcript variants have been described. A related pseudogene exists in chromosome 6. [provided by RefSeq, Mar 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033637.4. 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
	BTRC	NM_033637.4	MANE Select	c.37_39delCTCinsGTA	p.Leu13Val	missense	N/A	NP_378663.1	Q9Y297-1
	BTRC	NM_001256856.2		c.37_39delCTCinsGTA	p.Leu13Val	missense	N/A	NP_001243785.1	B7Z3H4
	BTRC	NM_003939.5		c.37_39delCTCinsGTA	p.Leu13Val	missense	N/A	NP_003930.1	Q9Y297-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTRC	ENST00000370187.8	TSL:1 MANE Select	c.37_39delCTCinsGTA	p.Leu13Val	missense	N/A	ENSP00000359206.3	Q9Y297-1
	BTRC	ENST00000393441.8	TSL:1	c.37_39delCTCinsGTA	p.Leu13Val	missense	N/A	ENSP00000377088.5	B7Z3H4
	BTRC	ENST00000408038.6	TSL:1	c.37_39delCTCinsGTA	p.Leu13Val	missense	N/A	ENSP00000385339.2	Q9Y297-2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.2

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: chr10-103113974;