M-14769-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BA1

The ENST00000361789.2(MT-CYB):c.23A>G(p.Asn8Ser) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Mitomap GenBank: 𝑓 0.011 (AC: 676)
• Consequence: MT-CYB ENST00000361789.2 missense
• Scores: Apogee2 Benign 0.033
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 6.93

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]

MT-TE (HGNC:7479): (mitochondrially encoded tRNA glutamic acid)

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.032791037 < 0.5 .
• BP6: Variant M-14769-A-G is Benign according to our data. Variant chrM-14769-A-G is described in ClinVar as [Benign]. Clinvar id is 693761.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: High frequency in mitomap database: 0.0111

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYTB	CYTB.1	c.23A>G	p.Asn8Ser	missense_variant	1/1
TRNE	TRNE.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-CYB	ENST00000361789.2	c.23A>G	p.Asn8Ser	missense_variant	1/1			P1
MT-TE	ENST00000387459.1			upstream_gene_variant

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.011 AC: 676

Gnomad homoplasmic AF: 0.040 AC: 2248 AN: 56387

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56387

Alfa AF: 0.0148 Hom.: 70

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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.14769A>G (YP_003024038.1:p.Asn8Ser) 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	0.033
Hmtvar	Pathogenic	0.67
AlphaMissense	Benign	0.087

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28357679; hg19: chrM-14770; COSMIC: COSV104419783; COSMIC: COSV104419783;