ENST00000361899.2:c.90G>T

Variant names:

• chrM-8616-G-T
• rs41427749
• ENST00000361899.2:c.90G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4 BP6_Very_Strong BS2

The ENST00000361899.2(MT-ATP6):​c.90G>T​(p.Leu30Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L30S) has been classified as Uncertain significance.

• Frequency: Mitomap GenBank: 𝑓 0.0035 (AC: 213)
• Consequence: MT-ATP6 ENST00000361899.2 missense
• Scores: Apogee2 Benign 0.15
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3 No linked disesase in Mitomap
• Conservation: PhyloP100: -2.25
• Publications: 11 publications found

Genes affected

MT-ATP6 (HGNC:7414): (mitochondrially encoded ATP synthase 6) Contributes to proton-transporting ATP synthase activity, rotational mechanism. Involved in mitochondrial ATP synthesis coupled proton transport. Part of mitochondrial proton-transporting ATP synthase complex. Implicated in Leber hereditary optic neuropathy; NARP syndrome; Parkinson's disease; multiple sclerosis; and systemic lupus erythematosus. [provided by Alliance of Genome Resources, Apr 2022]

MT-ATP8 (HGNC:7415): (mitochondrially encoded ATP synthase 8) Contributes to proton-transporting ATP synthase activity, rotational mechanism. Involved in mitochondrial ATP synthesis coupled proton transport. Part of mitochondrial proton-transporting ATP synthase complex. Implicated in multiple sclerosis and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

MT-ATP8 Gene-Disease associations (from GenCC):

• mitochondrial proton-transporting ATP synthase complex deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• periodic paralysis with later-onset distal motor neuropathy

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial disease

  Inheritance: AR, Mitochondrial Classification: LIMITED Submitted by: Illumina, ClinGen

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.15380181 < 0.5 .
• BP6: Variant M-8616-G-T is Benign according to our data. Variant chrM-8616-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 324

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361899.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-ATP6	ENST00000361899.2	TSL:6	c.90G>T	p.Leu30Phe	missense	Exon 1 of 1	ENSP00000354632.2	P00846
	MT-ATP8	ENST00000361851.1	TSL:6	c.*44G>T		downstream_gene	N/A	ENSP00000355265.1	P03928

Frequencies

Mitomap GenBank AF: 0.0035 AC: 213

Gnomad homoplasmic AF: 0.0057 AC: 324 AN: 56432

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56432

Alfa AF: 0.00446 Hom.: 20

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Leigh syndrome (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.15
Hmtvar	Pathogenic	0.76
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.23	T
DEOGEN2	Benign	0.055	T
LIST_S2	Benign	0.73	T
MutationAssessor	Benign	1.6	L
PhyloP100		-2.3
PROVEAN	Uncertain	-3.2	D
Sift4G	Uncertain	0.043	D
GERP RS		-7.5
Varity_R		0.60
Mutation Taster		=89/11	polymorphism

Other links and lift over

dbSNP: rs41427749; hg19: chrM-8617;