rs1556424448

chrM-14477-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The ENST00000361681.2(MT-ND6):c.197T>C(p.Val66Ala) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 2)
• Consequence: MT-ND6 ENST00000361681.2 missense
• Scores: Apogee2 Pathogenic 0.76
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 5.72

Genes affected

MT-ND6 (HGNC:7462): (mitochondrially encoded NADH dehydrogenase 6) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Predicted to be located in mitochondrial inner membrane. Implicated in Leber hereditary optic neuropathy; Leigh disease; and spinal muscular atrophy with lower extremity predominante 2B. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a transmembrane_region Helical (size 20) in uniprot entity NU6M_HUMAN there are 5 pathogenic changes around while only 1 benign (83%) in ENST00000361681.2
• PM2: Very low frequency in mitomap database: 0.0
• PP3: Apogee2 supports a deletorius effect, 0.75750566 >= 0.5 .

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-ND6	ENST00000361681.2	c.197T>C	p.Val66Ala	missense_variant	1/1			P1

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap GenBank AF: 0.0 AC: 2

Gnomad homoplasmic AF: 0.0 AC: 0 AN: 56434

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56434

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Headache;C0030554:Paresthesia;C0037763:Muscle spasm;C0042571:Vertigo;C0235095:Constriction of peripheral visual field;C0338656:Cognitive impairment;C4021085:Abnormal brain morphology Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Jan 01, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Pathogenic	0.76
Hmtvar	Pathogenic	0.80
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.027	T
DEOGEN2	Pathogenic	0.85	D
LIST_S2	Benign	0.74	T
MutationAssessor	Pathogenic	3.5	H
MutationTaster	Benign	1.0	D
PROVEAN	Uncertain	-4.0	D
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
GERP RS		4.0
Varity_R		0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1556424448; hg19: chrM-14478;