ENST00000361789.2:c.1000A>G

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTB	unassigned_transcript_4818	c.1000A>G	p.Ile334Val	missense_variant	Exon 1 of 1
TRNT	unassigned_transcript_4819	c.-142A>G		upstream_gene_variant
TRNP	unassigned_transcript_4820	c.*210T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CYB	ENST00000361789.2	c.1000A>G	p.Ile334Val	missense_variant	Exon 1 of 1	6		ENSP00000354554.2
MT-TT	ENST00000387460.2	n.-142A>G		upstream_gene_variant		6
MT-TP	ENST00000387461.2	n.*210T>C		downstream_gene_variant		6

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leigh syndrome Benign:1

Oct 17, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.15746A>G (YP_003024038.1:p.Ile334Val) variant in MTCYB gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BA1 -

not provided Benign:1

Jun 02, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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;