rs386829260

Variant names:

• chrM-15746-A-G
• rs386829260
• ENST00000361789.2:c.1000A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BA1

The ENST00000361789.2(MT-CYB):​c.1000A>G​(p.Ile334Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 4/4 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. I334T) has been classified as Benign.

• Frequency: Mitomap GenBank: 𝑓 0.034 (AC: 2087)
• Consequence: MT-CYB ENST00000361789.2 missense
• Scores: Apogee2 Benign 0.0017
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.456
• Publications: 5 publications found

Genes affected

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]

TRNT (HGNC:7499): (mitochondrially encoded tRNA threonine)

TRNP (HGNC:7494): (mitochondrially encoded tRNA proline)

TRNP Gene-Disease associations (from GenCC):

• MERRF syndrome

  Inheritance: Mitochondrial Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.0017165771 < 0.5 .
• BP6: Variant M-15746-A-G is Benign according to our data. Variant chrM-15746-A-G is described in ClinVar as Benign. ClinVar VariationId is 235623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: High frequency in mitomap database: 0.0341

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361789.2. 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-CYB	ENST00000361789.2	TSL:6	c.1000A>G	p.Ile334Val	missense	Exon 1 of 1	ENSP00000354554.2	P00156
	MT-TT	ENST00000387460.2	TSL:6	n.-142A>G		upstream_gene	N/A
	MT-TP	ENST00000387461.2	TSL:6	n.*210T>C		downstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.034 AC: 2087

Gnomad homoplasmic AF: 0.0024 AC: 133 AN: 56431

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56431

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.0017
Hmtvar	Benign	0.080
AlphaMissense	Benign	0.087
PhyloP100		0.46
Mutation Taster		=78/22	polymorphism

Other links and lift over

dbSNP: rs386829260; hg19: chrM-15747;