rs782001959

Positions:

• chrX-155492384-C-A

Variant summary

Our verdict is Likely benign. Variant got -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, single submitter U:1 O:1
• Conservation: PhyloP100: 0.251

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

Verdict is Likely_benign. Variant got -4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMLHE	NM_018196.4	c.1107G>T	p.Glu369Asp	missense_variant	7/8	ENST00000334398.8	NP_060666.1
TMLHE-AS1	NR_039991.1	n.472-496C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMLHE	ENST00000334398.8	c.1107G>T	p.Glu369Asp	missense_variant	7/8	1	NM_018196.4	ENSP00000335261	P1
TMLHE-AS1	ENST00000452506.1	n.67+2995C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.00206 AC: 37 AN: 17990 Hom.: 1 AF XY: 0.000246 AC XY: 1 AN XY: 4070

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 SAS 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

Significance: Uncertain significance

Submissions summary: Uncertain:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Epsilon-trimethyllysine hydroxylase deficiency Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Oct 23, 2012

- -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	D
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs782001959; hg19: chrX-154722045;