chrX-155507098-AGT-TGA

Variant names:

• chrX-155507098-AGT-TGA
• NM_018196.4:c.793_795delACTinsTCA
• TMLHE p.Thr265Ser

Variant summary

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

The NM_018196.4(TMLHE):​c.793_795delACTinsTCA​(p.Thr265Ser) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T265I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: TMLHE NM_018196.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.57
• Publications: 0 publications found

Genes affected

TMLHE (HGNC:18308): (trimethyllysine hydroxylase, epsilon) This gene encodes the protein trimethyllysine dioxygenase which is the first enzyme in the carnitine biosynthesis pathway. Carnitine play an essential role in the transport of activated fatty acids across the inner mitochondrial membrane. The encoded protein converts trimethyllysine into hydroxytrimethyllysine. A pseudogene of this gene is found on chromosome X. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

TMLHE-AS1 (HGNC:44261): (TMLHE antisense RNA 1)

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_018196.4. 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
	TMLHE	NM_018196.4	MANE Select	c.793_795delACTinsTCA	p.Thr265Ser	missense	N/A	NP_060666.1	Q9NVH6-1
	TMLHE	NM_001184797.2		c.793_795delACTinsTCA	p.Thr265Ser	missense	N/A	NP_001171726.1	Q9NVH6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMLHE	ENST00000334398.8	TSL:1 MANE Select	c.793_795delACTinsTCA	p.Thr265Ser	missense	N/A	ENSP00000335261.3	Q9NVH6-1
	TMLHE	ENST00000369439.4	TSL:1	c.793_795delACTinsTCA	p.Thr265Ser	missense	N/A	ENSP00000358447.4	Q9NVH6-2
	TMLHE	ENST00000902557.1		c.862_864delACTinsTCA	p.Thr288Ser	missense	N/A	ENSP00000572616.1

Frequencies

GnomAD3 genomes Cov.: 22

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

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.6

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: chrX-154736759;