rs199951903

chrM-15497-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM5 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G251D) has been classified as Likely pathogenic.

• 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

Genes affected

CYTB (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.
• 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 [Likely_benign]. Clinvar id 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/exons	MANE	UniProt
CYTB	CYTB.1	c.751G>A	p.Gly251Ser	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-CYB	ENST00000361789.2	c.751G>A	p.Gly251Ser	missense_variant	1/1			P1

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

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: 0.00333 Hom.: 21

Mitomap

EXIT-/-Obesity

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

Benign, criteria provided, single submitter

clinical testing

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

Oct 17, 2019

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

Likely benign, criteria provided, single submitter

clinical testing

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

Jan 04, 2017

- -

Obesity Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Oct 01, 2003

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.053
Hmtvar	Benign	0.22
AlphaMissense	Benign	0.10

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs199951903; hg19: chrM-15498;