M-14750-A-T

Variant names:

• chrM-14750-A-T
• rs1603224853
• unassigned_transcript_4818:c.4A>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 4)
• Consequence: CYTB missense
• Scores: Apogee2 Benign 0.052
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 1.22

Genes affected

CYTB (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]

ND6 (HGNC:7462): (mitochondrially encoded NADH dehydrogenase 6) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Predicted to be located in mitochondrial inner membrane. Implicated in Leber hereditary optic neuropathy; Leigh disease; and spinal muscular atrophy with lower extremity predominante 2B. [provided by Alliance of Genome Resources, Apr 2022]

TRNE (HGNC:7479): (mitochondrially encoded tRNA glutamic acid)

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant M-14750-A-T is Benign according to our data. Variant chrM-14750-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 693755.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 8

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTB	unassigned_transcript_4818	c.4A>T	p.Thr2Ser	missense_variant	Exon 1 of 1
ND6	unassigned_transcript_4816	c.-77T>A		upstream_gene_variant
TRNE	unassigned_transcript_4817	c.-8T>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.00010 AC: 4

Gnomad homoplasmic AF: 0.00014 AC: 8 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Benign:1

Oct 17, 2019

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.14750A>T (YP_003024038.1:p.Thr2Ser) variant in MTCYB gene is interpretated to be a Likely Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BP4, BP6 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.052
Hmtvar	Benign	0.080
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: rs1603224853; hg19: chrM-14751;