rs782001959

Variant names:

• chrX-155492384-C-A
• rs782001959
• NM_018196.4:c.1107G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018196.4(TMLHE):​c.1107G>T​(p.Glu369Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: TMLHE NM_018196.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2 O:1
• Conservation: PhyloP100: 0.251
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01514402).

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.1107G>T	p.Glu369Asp	missense	Exon 7 of 8	NP_060666.1	Q9NVH6-1
	TMLHE-AS1	NR_039991.1		n.472-496C>A		intron	N/A
	TMLHE	NM_001184797.2		c.*181G>T		downstream_gene	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.1107G>T	p.Glu369Asp	missense	Exon 7 of 8	ENSP00000335261.3	Q9NVH6-1
	TMLHE-AS1	ENST00000433624.1	TSL:1	n.472-496C>A		intron	N/A
	TMLHE	ENST00000902557.1		c.1176G>T	p.Glu392Asp	missense	Exon 8 of 9	ENSP00000572616.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.00206 AC: 37 AN: 17990 AF XY: 0.000246

Gnomad AFR exome AF: 0.0115

Gnomad AMR exome AF: 0.000498

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.000499 Hom.: 0

ExAC AF: 0.000901 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	not specified (1)
-	-	-	Epsilon-trimethyllysine hydroxylase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Uncertain	0.090
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.62	D
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.015	T
MetaSVM	Uncertain	0.059	D
MutationAssessor	Pathogenic	3.4	M
PhyloP100		0.25
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.5	D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.024	D
Polyphen		1.0	D
Vest4		0.80
MutPred		0.48		Loss of catalytic residue at W371 (P = 0.0826)
MVP		0.54
MPC		0.82
ClinPred		0.16	T
GERP RS		1.4
Varity_R		0.57
gMVP		0.44
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs782001959; hg19: chrX-154722045;