rs12557310

Positions:

• chrX-155506037-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018196.4(TMLHE):​c.995+861A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 109,961 control chromosomes in the GnomAD database, including 14,286 homozygotes. There are 17,945 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (14286 hom., 17945 hem., cov: 22)
• Consequence: TMLHE NM_018196.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMLHE	NM_018196.4	c.995+861A>G		intron_variant		ENST00000334398.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMLHE	ENST00000334398.8	c.995+861A>G		intron_variant		1	NM_018196.4	P1
TMLHE	ENST00000369439.4	c.995+861A>G		intron_variant		1
TMLHE-AS1	ENST00000452506.1	n.67+16648T>C		intron_variant, non_coding_transcript_variant		5
TMLHE	ENST00000675642.1	c.1028+861A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.551 AC: 60555 AN: 109908 Hom.: 14290 Cov.: 22 AF XY: 0.555 AC XY: 17927 AN XY: 32314

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.579

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.551 AC: 60552 AN: 109961 Hom.: 14286 Cov.: 22 AF XY: 0.554 AC XY: 17945 AN XY: 32377

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.722

Gnomad4 OTH AF: 0.572

Alfa AF: 0.690 Hom.: 55649

Bravo AF: 0.529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.82

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

LitVar

Other links and lift over

dbSNP: rs12557310; hg19: chrX-154735698;