X-155524585-G-T

Variant names:

• chrX-155524585-G-T
• rs781889971
• NM_018196.4:c.229C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_018196.4(TMLHE):​c.229C>A​(p.Arg77Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000917 in 1,090,146 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.2e-7 (0 hom. 1 hem.)
• Consequence: TMLHE NM_018196.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=1.8 with no splicing effect.

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.229C>A	p.Arg77Arg	synonymous	Exon 3 of 8	NP_060666.1	Q9NVH6-1
	TMLHE	NM_001184797.2		c.229C>A	p.Arg77Arg	synonymous	Exon 3 of 7	NP_001171726.1	Q9NVH6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMLHE	ENST00000334398.8	TSL:1 MANE Select	c.229C>A	p.Arg77Arg	synonymous	Exon 3 of 8	ENSP00000335261.3	Q9NVH6-1
	TMLHE	ENST00000369439.4	TSL:1	c.229C>A	p.Arg77Arg	synonymous	Exon 3 of 7	ENSP00000358447.4	Q9NVH6-2
	TMLHE	ENST00000902557.1		c.298C>A	p.Arg100Arg	synonymous	Exon 4 of 9	ENSP00000572616.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.17e-7 AC: 1 AN: 1090146 Hom.: 0 Cov.: 30 AF XY: 0.00000281 AC XY: 1 AN XY: 356318

African (AFR) AF: 0.00 AC: 0 AN: 26197

American (AMR) AF: 0.00 AC: 0 AN: 34524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19186

East Asian (EAS) AF: 0.00 AC: 0 AN: 29938

South Asian (SAS) AF: 0.0000192 AC: 1 AN: 52014

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4108

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 838069

Other (OTH) AF: 0.00 AC: 0 AN: 45766

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Benign	0.91
PhyloP100		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs781889971; hg19: chrX-154754246;