rs199795644

Variant names:

• chrM-14831-G-A
• rs199795644
• ENST00000361789.2:c.85G>A

Your query was ambiguous. Multiple possible variants found:

• chrM-14831-G-A
• chrM-14831-G-C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000361789.2(MT-CYB):​c.85G>A​(p.Ala29Thr) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A29V) has been classified as Likely benign.

• Frequency: Mitomap GenBank: 𝑓 0.0019 (AC: 115)
• Consequence: MT-CYB ENST00000361789.2 missense
• Scores: Apogee2 Benign 0.013
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1 LHON
• Conservation: PhyloP100: -1.78
• Publications: 12 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-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)

TRNE Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.013223543 < 0.5 .
• BP6: Variant M-14831-G-A is Benign according to our data. Variant chrM-14831-G-A is described in ClinVar as Benign. ClinVar VariationId is 65517.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 162

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTB	unassigned_transcript_4818	c.85G>A	p.Ala29Thr	missense_variant	Exon 1 of 1
ND6	unassigned_transcript_4816	c.-158C>T		upstream_gene_variant
TRNE	unassigned_transcript_4817	c.-89C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CYB	ENST00000361789.2	c.85G>A	p.Ala29Thr	missense_variant	Exon 1 of 1	6		ENSP00000354554.2
MT-ND6	ENST00000361681.2	c.-158C>T		upstream_gene_variant		6		ENSP00000354665.2
MT-TE	ENST00000387459.1	n.-89C>T		upstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.0019 AC: 115

Gnomad homoplasmic AF: 0.0029 AC: 162 AN: 56375

Gnomad heteroplasmic AF: 0.00028 AC: 16 AN: 56375

Alfa AF: 0.00353 Hom.: 79

Mitomap

Disease(s): LHON

Status: Reported

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other: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: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.14831G>A (YP_003024038.1:p.Ala29Thr) 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 -

Leber optic atrophy Other:1

-

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.013
Hmtvar	Benign	0.12
AlphaMissense	Benign	0.082
PhyloP100		-1.8
Mutation Taster		=92/8	polymorphism

Other links and lift over

dbSNP: rs199795644; hg19: chrM-14832;