5-157731577-CC-TA

Variant names:

• chr5-157731577-CC-TA
• NM_017872.5:c.137_138delCCinsTA
• THG1L p.Thr46Ile

Variant summary

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

The NM_017872.5(THG1L):​c.137_138delCCinsTA​(p.Thr46Ile) 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. T46S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: THG1L NM_017872.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.50
• Publications: 0 publications found

Genes affected

THG1L (HGNC:26053): (tRNA-histidine guanylyltransferase 1 like) The protein encoded by this gene is a mitochondrial protein that is induced by high levels of glucose and is associated with diabetic nephropathy. The encoded protein appears to increase mitochondrial biogenesis, which could lead to renal fibrosis. Another function of this protein is that of a guanyltransferase, adding GMP to the 5' end of tRNA(His). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

THG1L Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive 28

  Inheritance: AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

ENSG00000309117 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017872.5. 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
	THG1L	NM_017872.5	MANE Select	c.137_138delCCinsTA	p.Thr46Ile	missense	N/A	NP_060342.2	Q9NWX6
	THG1L	NM_001317825.2		c.-235_-234delCCinsTA		5_prime_UTR	Exon 1 of 6	NP_001304754.1	Q9H8R6
	THG1L	NM_001317824.2		c.-165_-164delCCinsTA		5_prime_UTR	Exon 1 of 6	NP_001304753.1	B4E366

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THG1L	ENST00000231198.12	TSL:1 MANE Select	c.137_138delCCinsTA	p.Thr46Ile	missense	N/A	ENSP00000231198.7	Q9NWX6
	THG1L	ENST00000884966.1		c.137_138delCCinsTA	p.Thr46Ile	missense	N/A	ENSP00000555025.1
	THG1L	ENST00000960054.1		c.137_138delCCinsTA	p.Thr46Ile	missense	N/A	ENSP00000630113.1

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		4.5

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: chr5-157158585;