rs1057520099

Variant names:

• chrM-12175-T-C
• rs1057520099
• unassigned_transcript_4812:c.38T>C
• TRNH p.Leu13Pro

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS2

The ENST00000000000(TRNH):​c.38T>C​(p.Leu13Pro) variant causes a missense change. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency: Mitomap GenBank: 𝑓 0.00060 (AC: 35)
• Consequence: TRNH ENST00000000000 missense
• Scores: Mitotip Benign 6.8
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 5.78
• Publications: 1 publications found

Genes affected

TRNH (HGNC:7487): (mitochondrially encoded tRNA histidine)

MT-ND5 (HGNC:7461): (mitochondrially encoded NADH dehydrogenase 5) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Leigh disease; and MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND4 (HGNC:7459): (mitochondrially encoded NADH dehydrogenase 4) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Parkinson's disease; macular degeneration; and schizophrenia. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

TRNL2 (HGNC:7491): (mitochondrially encoded tRNA leucine 2 (CUN))

TRNS2 (HGNC:7498): (mitochondrially encoded tRNA serine 2 (AGU/C))

TRNS2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP6: Variant M-12175-T-C is Benign according to our data. Variant chrM-12175-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 376964.
• BS2: High AC in GnomadMitoHomoplasmic at 14

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387441.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-TH	ENST00000387441.1	TSL:6	n.38T>C		non_coding_transcript_exon	Exon 1 of 1
	MT-ND5	ENST00000361567.2	TSL:6	c.-162T>C		upstream_gene	N/A	ENSP00000354813.2	P03915
	MT-ND4	ENST00000361381.2	TSL:6	c.*38T>C		downstream_gene	N/A	ENSP00000354961.2	P03905

Frequencies

Mitomap GenBank AF: 0.00060 AC: 35

Gnomad homoplasmic AF: 0.00025 AC: 14 AN: 56433

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56433

Alfa AF: 0.000334 Hom.: 1

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	MELAS syndrome (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	6.8
Hmtvar	Benign	0.050
PhyloP100		5.8

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1057520099; hg19: chrM-12176;