chrX-155491566-T-C

Variant names:

• chrX-155491566-T-C
• NM_018196.4:c.1235A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018196.4(TMLHE):​c.1235A>G​(p.Asn412Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 5)
• Consequence: TMLHE NM_018196.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.59
• Publications: 0 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1284349).

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.1235A>G	p.Asn412Ser	missense	Exon 8 of 8	NP_060666.1	Q9NVH6-1
	TMLHE-AS1	NR_039991.1		n.472-1314T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMLHE	ENST00000334398.8	TSL:1 MANE Select	c.1235A>G	p.Asn412Ser	missense	Exon 8 of 8	ENSP00000335261.3	Q9NVH6-1
	TMLHE-AS1	ENST00000433624.1	TSL:1	n.472-1314T>C		intron	N/A
	TMLHE	ENST00000902557.1		c.1304A>G	p.Asn435Ser	missense	Exon 9 of 9	ENSP00000572616.1

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD4 exome Cov.: 5

GnomAD4 genome Cov.: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.9
DANN	Benign	0.84
DEOGEN2	Benign	0.14	T
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	-1.9	N
PhyloP100		2.6
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.93	N
REVEL	Benign	0.25
Sift	Benign	0.91	T
Sift4G	Benign	1.0	T
Polyphen		0.25	B
Vest4		0.16
MutPred		0.72		Gain of disorder (P = 0.0741)
MVP		0.66
MPC		0.19
ClinPred		0.13	T
GERP RS		2.4
Varity_R		0.090
gMVP		0.16
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

hg19: chrX-154721227;