M-14750-A-G

Position:

• chrM-14750-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000361789.2(MT-CYB):​c.4A>G​(p.Thr2Ala) 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 (★).

• Frequency: Mitomap GenBank: 𝑓 0.00080 (AC: 46)
• Consequence: MT-CYB ENST00000361789.2 missense
• Scores: Apogee2 Benign 0.032
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 1.22

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 -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.032305054 < 0.5 .
• BP6: Variant M-14750-A-G is Benign according to our data. Variant chrM-14750-A-G is described in ClinVar as [Benign]. Clinvar id is 693754.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 53

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYTB	CYTB.1	c.4A>G	p.Thr2Ala	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.4A>G	p.Thr2Ala	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: 0.00080 AC: 46

Gnomad homoplasmic AF: 0.00094 AC: 53 AN: 56425

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56425

Alfa AF: 0.00100 Hom.: 4

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.14750A>G (YP_003024038.1:p.Thr2Ala) 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, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.032
Hmtvar	Benign	0.050
AlphaMissense	Benign	0.082

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603224853; hg19: chrM-14751;