M-10506-A-G

Position:

• chrM-10506-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000361335.1(MT-ND4L):​c.37A>G​(p.Thr13Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T13I) has been classified as Likely benign.

• Frequency: Mitomap GenBank: 𝑓 0.0027 (AC: 168)
• Consequence: MT-ND4L ENST00000361335.1 missense
• Scores: Apogee2 Benign 0.036
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -6.00

Genes affected

MT-ND4L (HGNC:7460): (mitochondrially encoded NADH 4L dehydrogenase) Predicted to enable NADH dehydrogenase (ubiquinone) activity. Predicted to be located in mitochondrial inner membrane. Implicated in Leber hereditary optic neuropathy and diabetes mellitus. [provided by Alliance of Genome Resources, Apr 2022]

MT-TR (HGNC:7496): (mitochondrially encoded tRNA arginine)

TRNR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.03628164 < 0.5 .
• BP6: Variant M-10506-A-G is Benign according to our data. Variant chrM-10506-A-G is described in ClinVar as [Benign]. Clinvar id is 693293.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 145

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNR	TRNR.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-ND4L	ENST00000361335.1	c.37A>G	p.Thr13Ala	missense_variant	1/1			ENSP00000354728	P1
MT-TR	ENST00000387439.1			downstream_gene_variant

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.0027 AC: 168

Gnomad homoplasmic AF: 0.0026 AC: 145 AN: 56429

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56429

Alfa AF: 0.00513 Hom.: 23

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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.10506A>G (YP_003024034.1:p.Thr13Ala) variant in MTND4L 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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.036
Hmtvar	Benign	0.10
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.47	T
DEOGEN2	Benign	0.033	T
LIST_S2	Benign	0.34	T
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-1.1	N
Sift	Benign	0.16	T
Sift4G	Benign	0.46	T
GERP RS		-10
Varity_R		0.13

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs199688733; hg19: chrM-10507;