rs1057520074

Variant names:

• chrM-10499-A-G
• rs1057520074
• ENST00000361335.1:c.30A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BS1 BS2

The ENST00000361335.1(MT-ND4L):​c.30A>G​(p.Leu10Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0094 (AC: 574)
• Consequence: MT-ND4L ENST00000361335.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: -1.00
• Publications: 6 publications found

Genes affected

MT-ND4L (HGNC:7460): (mitochondrially encoded NADH 4L dehydrogenase) Predicted to enable NADH dehydrogenase (ubiquinone) activity. Predicted to be located in mitochondrial inner membrane. Implicated in Leber hereditary optic neuropathy and diabetes mellitus. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND3 (HGNC:7458): (mitochondrially encoded NADH dehydrogenase 3) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Leigh disease; and Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

TRNR (HGNC:7496): (mitochondrially encoded tRNA arginine)

TRNR Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP6: Variant M-10499-A-G is Benign according to our data. Variant chrM-10499-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 376866.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1 with no splicing effect.
• BS1: High frequency in mitomap database: 0.0094
• BS2: High AC in GnomadMitoHomoplasmic at 419

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361335.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-ND4L	ENST00000361335.1	TSL:6	c.30A>G	p.Leu10Leu	synonymous	Exon 1 of 1	ENSP00000354728.1
	MT-ND3	ENST00000361227.2	TSL:6	c.*95A>G		downstream_gene	N/A	ENSP00000355206.2
	MT-TR	ENST00000387439.1	TSL:6	n.*30A>G		downstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.0094 AC: 574

Gnomad homoplasmic AF: 0.0074 AC: 419 AN: 56433

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56433

Alfa AF: 0.0105 Hom.: 288

Mitomap

No disease associated.

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.0

Other links and lift over

dbSNP: rs1057520074; hg19: chrM-10500;