Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4BS2

The ENST00000361567.2(MT-ND5):c.157A>G(p.Met53Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Mitomap GenBank:

𝑓 0.0 ( AC: 3 )

Consequence

MT-ND5
ENST00000361567.2 missense

Scores

Apogee2

Benign

0.027

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

No linked disesase in Mitomap

Conservation

PhyloP100: -2.97

Publications

0 publications found

Variant links:

Genes affected

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-ND5 links:

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

TRNL2 links:

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

TRNS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very low frequency in mitomap database: 0.0

BP4

Apogee2 supports a benign effect, 0.027463935 < 0.5 .

BS2

High AC in GnomadMitoHomoplasmic at 4

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361567.2. 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MT-ND5	ENST00000361567.2	TSL:6	c.157A>G	p.Met53Val	missense	Exon 1 of 1	ENSP00000354813.2
MT-TS2	ENST00000387449.1	TSL:6	n.*228A>G		downstream_gene	N/A
MT-TL2	ENST00000387456.1	TSL:6	n.*157A>G		downstream_gene	N/A

Frequencies

Mitomap GenBank

AF:

0.0

AC:

Gnomad homoplasmic

AF:

0.000071

AC:

AN:

56432

Gnomad heteroplasmic

AF:

0.000018

AC:

AN:

56432

Alfa

AF:

0.000223

Hom.:

Mitomap

No disease associated.

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

Apogee2

Benign

0.027

Hmtvar

Benign

0.21

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.58

PhyloP100

-3.0

GERP RS

-6.5

Varity_R

0.24

Mutation Taster

=43/157

disease causing

(source)

Publications

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rs1556424118

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Mitomap

ClinVar

ClinVar submissions as Germline

Computational scores

Publications

Other links and lift over