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

Scores

3
8
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1O:1

Conservation

PhyloP100: 0.251
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 UniProt
TMLHENM_018196.4 linkuse as main transcriptc.1107G>T p.Glu369Asp missense_variant 7/8 ENST00000334398.8
TMLHE-AS1NR_039991.1 linkuse as main transcriptn.472-496C>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TMLHEENST00000334398.8 linkuse as main transcriptc.1107G>T p.Glu369Asp missense_variant 7/81 NM_018196.4 P1Q9NVH6-1
TMLHE-AS1ENST00000452506.1 linkuse as main transcriptn.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
show subpopulations
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:1Other:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingMendelicsMay 04, 2022- -
Epsilon-trimethyllysine hydroxylase deficiency Other:1
risk factor, no assertion criteria providedliterature onlyOMIMOct 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs782001959; hg19: chrX-154722045; API