5-175968089-CTC-TTT

Variant names:

• chr5-175968089-CTC-TTT
• NM_032361.4:c.118_120delGAGinsAAA
• THOC3 p.Glu40Lys

Variant summary

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

The NM_032361.4(THOC3):​c.118_120delGAGinsAAA​(p.Glu40Lys) 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 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: THOC3 NM_032361.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.75
• Publications: 0 publications found

Genes affected

THOC3 (HGNC:19072): (THO complex subunit 3) This gene encodes a component of the nuclear THO transcription elongation complex, which is part of the larger transcription export (TREX) complex that couples messenger RNA processing and export. In humans, the transcription export complex is recruited to the 5'-end of messenger RNAs in a splicing- and cap-dependent manner. Studies of a related complex in mouse suggest that the metazoan transcription export complex is involved in cell differentiation and development. A pseudogene of this gene has been defined on chromosome 5. [provided by RefSeq, May 2013]

ENSG00000296908 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032361.4. 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
	THOC3	NM_032361.4	MANE Select	c.118_120delGAGinsAAA	p.Glu40Lys	missense	N/A	NP_115737.1	Q96J01-1
	THOC3	NM_001376902.1		c.118_120delGAGinsAAA	p.Glu40Lys	missense	N/A	NP_001363831.1	Q96J01-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THOC3	ENST00000265097.9	TSL:1 MANE Select	c.118_120delGAGinsAAA	p.Glu40Lys	missense	N/A	ENSP00000265097.5	Q96J01-1
	THOC3	ENST00000513482.1	TSL:1	c.118_120delGAGinsAAA	p.Glu40Lys	missense	N/A	ENSP00000422243.1	Q96J01-2
	THOC3	ENST00000928778.1		c.118_120delGAGinsAAA	p.Glu40Lys	missense	N/A	ENSP00000598837.1

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		5.8

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: chr5-175395092;