M-14002-A-G

Position:

• chrM-14002-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0023 (AC: 143)
• Consequence: ND5 missense
• Scores: Apogee2 Benign 0.054
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 High-altitude-pulmonary-edema-susceptibility
• Conservation: PhyloP100: -0.389

Genes affected

ND5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant M-14002-A-G is Benign according to our data. Variant chrM-14002-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 445967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 185

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ND5	unassigned_transcript_4816	c.1666A>G	p.Thr556Ala	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.0023 AC: 143

Gnomad homoplasmic AF: 0.0033 AC: 185 AN: 56411

Gnomad heteroplasmic AF: 0.000089 AC: 5 AN: 56411

Alfa AF: 0.00356 Hom.: 16

Mitomap

High-altitude-pulmonary-edema-susceptibility

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leigh syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Oct 17, 2019

The NC_012920.1:m.14002A>G (YP_003024036.1:p.Thr556Ala) variant in MTND5 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished).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

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Mar 09, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.054
Hmtvar	Benign	0.14
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.52	T
DEOGEN2	Benign	0.029	T
LIST_S2	Benign	0.079	T
MutationAssessor	Benign	0.95	L
PROVEAN	Benign	-1.5	N
Sift4G	Benign	0.11	T
GERP RS		-0.43
Varity_R		0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs386829198; hg19: chrM-14003;