ENST00000361390.2:c.32T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4BP6_Very_StrongBS2

The ENST00000361390.2(MT-ND1):​c.32T>C​(p.Val11Ala) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V11I) has been classified as Benign.

Frequency

Mitomap GenBank:
𝑓 0.0021 ( AC: 126 )

Consequence

MT-ND1
ENST00000361390.2 missense

Scores

Apogee2
Benign
0.10

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
No linked disesase in Mitomap

Conservation

PhyloP100: 4.72

Publications

7 publications found
Variant links:
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

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ACMG classification

Classification was made for transcript

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

BP4
Apogee2 supports a benign effect, 0.10266045 < 0.5 .
BP6
Variant M-3338-T-C is Benign according to our data. Variant chrM-3338-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 692338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomadMitoHomoplasmic at 108

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ND1unassigned_transcript_4789 c.32T>C p.Val11Ala missense_variant Exon 1 of 1
TRNL1unassigned_transcript_4788 c.*34T>C downstream_gene_variant
RNR2unassigned_transcript_4787 n.*109T>C downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MT-ND1ENST00000361390.2 linkc.32T>C p.Val11Ala missense_variant Exon 1 of 1 6 ENSP00000354687.2 P03886
MT-TL1ENST00000386347.1 linkn.*34T>C downstream_gene_variant 6
MT-RNR2ENST00000387347.2 linkn.*109T>C downstream_gene_variant 6

Frequencies

Mitomap GenBank
AF:
0.0021
AC:
126
Gnomad homoplasmic
AF:
0.0019
AC:
108
AN:
56427
Gnomad heteroplasmic
AF:
0.000071
AC:
4
AN:
56427
Alfa
AF:
0.00169
Hom.:
82

Mitomap

No disease associated.

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Feb 16, 2025
Laboratory of Genetics, Children's Clinical University Hospital Latvia
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Leigh syndrome Benign:1
Oct 17, 2019
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The NC_012920.1:m.3338T>C (YP_003024026.1:p.Val11Ala) variant in MTND1 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BS2, BP4 -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Apogee2
Benign
0.10
Hmtvar
Benign
0.16
AlphaMissense
Benign
0.30
BayesDel_addAF
Benign
-0.55
T
DEOGEN2
Benign
0.095
T
LIST_S2
Benign
0.29
T
MutationAssessor
Benign
-0.0050
N
PhyloP100
4.7
PROVEAN
Uncertain
-3.2
D
Sift4G
Benign
0.075
T
GERP RS
4.5
Varity_R
0.43

Publications

Other links and lift over

dbSNP: rs201969351; hg19: chrM-3339; API