rs1057516074

Variant names:

• chrM-15127-C-T
• rs1057516074
• ENST00000361789.2:c.381C>T
• MT-CYB p.Ala127Ala

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP7

The ENST00000361789.2(MT-CYB):​c.381C>T​(p.Ala127Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 2)
• Consequence: MT-CYB ENST00000361789.2 synonymous
• Clinical Significance: Uncertain significance no assertion criteria provided U:2 No linked disesase in Mitomap
• Conservation: PhyloP100: -7.49
• Publications: 0 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-CYB Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial complex III deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BP7: Synonymous conserved (PhyloP=-7.49 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361789.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-CYB	ENST00000361789.2	TSL:6	c.381C>T	p.Ala127Ala	synonymous	Exon 1 of 1	ENSP00000354554.2	P00156

Frequencies

Mitomap GenBank AF: 0.0 AC: 2

Gnomad homoplasmic AF: 0.000035 AC: 2 AN: 56433

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56433

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Ataxia;C0018784:Sensorineural hearing loss disorder;C0234632:Reduced visual acuity;na:Atrophy of the brain and cerebellum (1)
-	1	-	Parkinsonism-plus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-7.5

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1057516074;

hg19: chrM-15128;