rs387906730

Variant names:

• chrM-3388-C-A
• rs387906730
• ENST00000361390.2:c.82C>A

Your query was ambiguous. Multiple possible variants found:

• chrM-3388-C-A
• chrM-3388-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4 BP6_Very_Strong BS2

The ENST00000361390.2(MT-ND1):​c.82C>A​(p.Leu28Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.00050 (AC: 30)
• Consequence: MT-ND1 ENST00000361390.2 missense
• Scores: Apogee2 Benign 0.39
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 U:1 B:2 Materally-Inherited-Nonsyndromic-Deafness
• Conservation: PhyloP100: -2.21
• Publications: 7 publications found

Genes affected

MT-ND1 (HGNC:7455): (mitochondrially encoded NADH dehydrogenase 1) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Located in mitochondrial membrane. Part of mitochondrial respiratory chain complex I. Implicated in several diseases, including MELAS syndrome; neurodegenerative disease (multiple); optic nerve disease (multiple); toxic shock syndrome; and type 2 diabetes mellitus. Biomarker of Alzheimer's disease; Parkinson's disease; and multiple sclerosis. [provided by Alliance of Genome Resources, Apr 2022]

TRNL1 (HGNC:7490): (mitochondrially encoded tRNA leucine 1 (UUA/G)) Implicated in cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

MT-RNR2 (HGNC:7471): (mitochondrially encoded 16S RNA) Enables G protein-coupled receptor binding activity; protein self-association; and receptor antagonist activity. Involved in several processes, including leukocyte chemotaxis; negative regulation of cell death; and negative regulation of neuroinflammatory response. Located in several cellular components, including mitochondrion; perinuclear region of cytoplasm; and sperm midpiece. [provided by Alliance of Genome Resources, Apr 2022]

MT-RNR2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.39391762 < 0.5 .
• BP6: Variant M-3388-C-A is Benign according to our data. Variant chrM-3388-C-A is described in ClinVar as Benign. ClinVar VariationId is 29998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 42

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361390.2. 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-ND1	ENST00000361390.2	TSL:6	c.82C>A	p.Leu28Met	missense	Exon 1 of 1	ENSP00000354687.2	P03886
	MT-TL1	ENST00000386347.1	TSL:6	n.*84C>A		downstream_gene	N/A
	MT-RNR2	ENST00000387347.2	TSL:6	n.*159C>A		downstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.00050 AC: 30

Gnomad homoplasmic AF: 0.00074 AC: 42 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Alfa AF: 0.000618 Hom.: 10

Mitomap

Disease(s): Materally-Inherited-Nonsyndromic-Deafness

Status: Reported

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Leigh syndrome (1)
1	-	-	Mitochondrial non-syndromic sensorineural hearing loss (1)
-	-	1	not provided (1)
-	1	-	Optic atrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.39
Hmtvar	Pathogenic	0.81
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.0048	T
DEOGEN2	Benign	0.041	T
LIST_S2	Uncertain	0.91	D
MutationAssessor	Benign	1.6	L
PhyloP100		-2.2
PROVEAN	Benign	-1.7	N
GERP RS		-9.1
Varity_R		0.56
Mutation Taster		=48/52	disease causing

Other links and lift over

dbSNP: rs387906730; hg19: chrM-3389;