ENST00000361789.2:c.511G>A

Variant names:

• chrM-15257-G-A
• rs41518645
• ENST00000361789.2:c.511G>A

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.511G>A​(p.Asp171Asn) variant causes a missense change. 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. D171S) has been classified as Uncertain significance.

• Frequency: Mitomap GenBank: 𝑓 0.015 (AC: 934)
• Consequence: MT-CYB ENST00000361789.2 missense
• Scores: Apogee2 Benign 0.17
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1 U:1 B:2 LHON
• Conservation: PhyloP100: 6.10
• Publications: 37 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]

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

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial complex III deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Apogee2 supports a benign effect, 0.17390026 < 0.5 .
• BP6: Variant M-15257-G-A is Benign according to our data. Variant chrM-15257-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 9674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: High frequency in mitomap database: 0.0153

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTB	unassigned_transcript_4818	c.511G>A	p.Asp171Asn	missense_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CYB	ENST00000361789.2	c.511G>A	p.Asp171Asn	missense_variant	Exon 1 of 1	6		ENSP00000354554.2

Frequencies

Mitomap GenBank AF: 0.015 AC: 934

Gnomad homoplasmic AF: 0.013 AC: 719 AN: 56424

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56424

Alfa AF: 0.0156 Hom.: 727

Mitomap

Disease(s): LHON

Status: Conflicting-reports

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1 Uncertain:1 Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leber optic atrophy Pathogenic:1 Uncertain:1

Aug 01, 1996

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Sep 19, 2013

GeneReviews

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: curation

- -

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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.15257G>A (YP_003024038.1:p.Asp171Asn) 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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.17
Hmtvar	Benign	0.24
AlphaMissense	Benign	0.12
PhyloP100		6.1

Other links and lift over

dbSNP: rs41518645; hg19: chrM-15258; COSMIC: COSV62378578; COSMIC: COSV62378578;