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, single submitter U:1 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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMLHE	NM_018196.4	c.1107G>T	p.Glu369Asp	missense_variant	Exon 7 of 8	ENST00000334398.8	NP_060666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMLHE	ENST00000334398.8	c.1107G>T	p.Glu369Asp	missense_variant	Exon 7 of 8	1	NM_018196.4	ENSP00000335261.3

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

Significance: Uncertain significance

Submissions summary: Uncertain:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 04, 2022

Mendelics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Epsilon-trimethyllysine hydroxylase deficiency Other:1

Oct 23, 2012

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

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
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;