rs12557310

Variant names:

• chrX-155506037-T-C
• rs12557310
• NM_018196.4:c.995+861A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMLHE	NM_018196.4	c.995+861A>G		intron_variant	Intron 6 of 7	ENST00000334398.8	NP_060666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMLHE	ENST00000334398.8	c.995+861A>G		intron_variant	Intron 6 of 7	1	NM_018196.4	ENSP00000335261.3

Frequencies

GnomAD3 genomes AF: 0.551 AC: 60555 AN: 109908 Hom.: 14290 Cov.: 22

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

African (AFR) AF: 0.147 AC: 4495 AN: 30570

American (AMR) AF: 0.614 AC: 6285 AN: 10237

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 1929 AN: 2615

East Asian (EAS) AF: 0.724 AC: 2481 AN: 3429

South Asian (SAS) AF: 0.679 AC: 1764 AN: 2597

European-Finnish (FIN) AF: 0.746 AC: 4296 AN: 5757

Middle Eastern (MID) AF: 0.778 AC: 168 AN: 216

European-Non Finnish (NFE) AF: 0.722 AC: 37844 AN: 52393

Other (OTH) AF: 0.572 AC: 844 AN: 1476

Alfa AF: 0.634 Hom.: 71796

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
PhyloP100		-0.087
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs12557310; hg19: chrX-154735698;