rs199951903

Variant names:

• chrM-15497-G-A
• rs199951903
• ENST00000361789.2:c.751G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BS1 BS2

The ENST00000361789.2(MT-CYB):​c.751G>A​(p.Gly251Ser) 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. G251D) has been classified as Uncertain significance.

• Frequency: Mitomap GenBank: 𝑓 0.0055 (AC: 338)
• Consequence: MT-CYB ENST00000361789.2 missense
• Scores: Apogee2 Benign 0.053
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 O:1 EXIT-/-Obesity
• Conservation: PhyloP100: 5.32
• Publications: 16 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, 0.052852184 < 0.5 .
• BP6: Variant M-15497-G-A is Benign according to our data. Variant chrM-15497-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 9687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: High frequency in mitomap database: 0.0055
• BS2: High AC in GnomadMitoHomoplasmic at 218

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTB	unassigned_transcript_4818	c.751G>A	p.Gly251Ser	missense_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CYB	ENST00000361789.2	c.751G>A	p.Gly251Ser	missense_variant	Exon 1 of 1	6		ENSP00000354554.2

Frequencies

Mitomap GenBank AF: 0.0055 AC: 338

Gnomad homoplasmic AF: 0.0039 AC: 218 AN: 56417

Gnomad heteroplasmic AF: 0.000089 AC: 5 AN: 56417

Alfa AF: 0.00303 Hom.: 38

Mitomap

Disease(s): EXIT-/-Obesity

Status: Reported

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2 Other:1

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.15497G>A (YP_003024038.1:p.Gly251Ser) 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: BS1, BS2 -

not provided Benign:1

Jan 04, 2017

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Obesity Other:1

Oct 01, 2003

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.053
Hmtvar	Benign	0.22
AlphaMissense	Benign	0.10
PhyloP100		5.3
Mutation Taster		=36/64	disease causing

Other links and lift over

dbSNP: rs199951903; hg19: chrM-15498;