Genetic Variant TMLHE:p.Ile313Thr (chrX-155506955-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018196.4(TMLHE):c.938T>C(p.Ile313Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,097,102 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

TMLHE
NM_018196.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.12

Publications

0 publications found

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 links:

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

TMLHE-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10434273).

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.938T>C	p.Ile313Thr	missense	Exon 6 of 8	NP_060666.1	Q9NVH6-1
	TMLHE	NM_001184797.2		c.938T>C	p.Ile313Thr	missense	Exon 6 of 7	NP_001171726.1	Q9NVH6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMLHE	ENST00000334398.8	TSL:1 MANE Select	c.938T>C	p.Ile313Thr	missense	Exon 6 of 8	ENSP00000335261.3	Q9NVH6-1
TMLHE	ENST00000369439.4	TSL:1	c.938T>C	p.Ile313Thr	missense	Exon 6 of 7	ENSP00000358447.4	Q9NVH6-2
TMLHE	ENST00000902557.1		c.1007T>C	p.Ile336Thr	missense	Exon 7 of 9	ENSP00000572616.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097102

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363086

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26340

American (AMR)

AF:

0.00

AC:

AN:

35110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19335

East Asian (EAS)

AF:

0.00

AC:

AN:

30175

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54109

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40529

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4128

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841347

Other (OTH)

AF:

0.00

AC:

AN:

46029

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.096

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.83

M_CAP

Benign

0.044

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.24

PhyloP100

4.1

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.72

REVEL

Benign

0.20

Sift

Benign

0.46

Sift4G

Benign

0.70

Polyphen

0.0030

Vest4

0.21

MutPred

0.50

Loss of stability (P = 0.0116)

MVP

0.61

MPC

0.31

ClinPred

0.23

GERP RS

3.2

Varity_R

0.089

gMVP

0.37

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over