M-10530-G-A

Position:

• chrM-10530-G-A

Variant summary

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

The ENST00000361335.1(MT-ND4L):​c.61G>A​(p.Val21Met) 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 (★).

• Frequency: Mitomap GenBank: 𝑓 0.00020 (AC: 12)
• Consequence: MT-ND4L ENST00000361335.1 missense
• Scores: Apogee2 Benign 0.014
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.953

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.014326971 < 0.5 .
• BP6: Variant M-10530-G-A is Benign according to our data. Variant chrM-10530-G-A is described in ClinVar as [Benign]. Clinvar id is 693297.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 9

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-ND4L	ENST00000361335.1	c.61G>A	p.Val21Met	missense_variant	1/1			ENSP00000354728	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: 0.00020 AC: 12

Gnomad homoplasmic AF: 0.00016 AC: 9 AN: 56393

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56393

Alfa AF: 0.000223 Hom.: 1

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.10530G>A (YP_003024034.1:p.Val21Met) 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, BS4, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.014
Hmtvar	Benign	0.12
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.47	T
DEOGEN2	Benign	0.0084	T
LIST_S2	Benign	0.43	T
MutationTaster	Benign	1.0	N
PROVEAN	Benign	0.28	N
Sift	Benign	0.74	T
GERP RS		-9.8
Varity_R		0.086

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603222880; hg19: chrM-10531;