1-114405658-AA-GG

Variant names:

• chr1-114405658-AA-GG
• NM_015906.4:c.2519_2520delTTinsCC
• TRIM33 p.Ile840Thr

Variant summary

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

The NM_015906.4(TRIM33):​c.2519_2520delTTinsCC​(p.Ile840Thr) variant causes a missense change involving the alteration of a non-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 variant affecting the same amino acid position, but resulting in a different missense (i.e. I840S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TRIM33 NM_015906.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04
• Publications: 0 publications found

Genes affected

TRIM33 (HGNC:16290): (tripartite motif containing 33) The protein encoded by this gene is thought to be a transcriptional corepressor. However, molecules that interact with this protein have not yet been identified. The protein is a member of the tripartite motif family. This motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. Three alternatively spliced transcript variants for this gene have been described, however, the full-length nature of one variant has not been determined. [provided by RefSeq, Jul 2008]

TRIM33 Gene-Disease associations (from GenCC):

• developmental dysplasia of the hip

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015906.4. 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
	TRIM33	NM_015906.4	MANE Select	c.2519_2520delTTinsCC	p.Ile840Thr	missense	N/A	NP_056990.3
	TRIM33	NM_033020.3		c.2519_2520delTTinsCC	p.Ile840Thr	missense	N/A	NP_148980.2	Q9UPN9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM33	ENST00000358465.7	TSL:1 MANE Select	c.2519_2520delTTinsCC	p.Ile840Thr	missense	N/A	ENSP00000351250.2	Q9UPN9-1
	TRIM33	ENST00000369543.6	TSL:1	c.2519_2520delTTinsCC	p.Ile840Thr	missense	N/A	ENSP00000358556.2	Q9UPN9-2
	TRIM33	ENST00000925754.1		c.2612_2613delTTinsCC	p.Ile871Thr	missense	N/A	ENSP00000595813.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0

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: chr1-114948280;