rs1057516070

Variant names:

• chrM-14706-A-G
• rs1057516070
• unassigned_transcript_4817:c.37T>C
• TRNE p.Ser13Pro

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000000000(TRNE):​c.37T>C​(p.Ser13Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 3/3 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 8)
• Consequence: TRNE ENST00000000000 missense
• Scores: Mitotip Benign 1.9
• Clinical Significance: Benign criteria provided, single submitter U:2 B:1 O:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.312
• Publications: 0 publications found

Genes affected

TRNE (HGNC:7479): (mitochondrially encoded tRNA glutamic acid)

MT-CYB (HGNC:7427): (mitochondrially encoded cytochrome b) Predicted to enable metal ion binding activity. Predicted to be involved in several processes, including electron transport coupled proton transport; response to cobalamin; and response to glucagon. Located in mitochondrion. Implicated in ovarian carcinoma and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND6 (HGNC:7462): (mitochondrially encoded NADH dehydrogenase 6) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Predicted to be located in mitochondrial inner membrane. Implicated in Leber hereditary optic neuropathy; Leigh disease; and spinal muscular atrophy with lower extremity predominante 2B. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND6 Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: STRONG, SUPPORTIVE Submitted by: G2P, Orphanet
• Leber plus disease

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• maternally-inherited Leigh syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• MELAS syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant M-14706-A-G is Benign according to our data. Variant chrM-14706-A-G is described in ClinVar as Benign. ClinVar VariationId is 370060.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 7

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387459.1. 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-TE	ENST00000387459.1	TSL:6	n.37T>C		non_coding_transcript_exon	Exon 1 of 1
	MT-CYB	ENST00000361789.2	TSL:6	c.-41A>G		upstream_gene	N/A	ENSP00000354554.2	P00156
	MT-ND6	ENST00000361681.2	TSL:6	c.-33T>C		upstream_gene	N/A	ENSP00000354665.2	P03923

Frequencies

Mitomap GenBank AF: 0.00010 AC: 8

Gnomad homoplasmic AF: 0.00012 AC: 7 AN: 56431

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56431

Alfa AF: 0.000445 Hom.: 2

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Developmental delay (1)
-	-	1	MELAS syndrome (1)
-	1	-	Sudden death;C1838993:Episodic vomiting;na:Mild liver congestion (1)
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	1.9
Hmtvar	Benign	0.0
PhyloP100		-0.31

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1057516070;

hg19: chrM-14707;