ENST00000361789.2:c.325T>C

Variant names:

• chrM-15071-T-C
• rs199999794
• ENST00000361789.2:c.325T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4 BP6_Very_Strong BS2

The ENST00000361789.2(MT-CYB):​c.325T>C​(p.Tyr109His) 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 Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0018 (AC: 108)
• Consequence: MT-CYB ENST00000361789.2 missense
• Scores: Apogee2 Benign 0.073
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.200
• Publications: 6 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: Benign. The variant received -13 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.07268605 < 0.5 .
• BP6: Variant M-15071-T-C is Benign according to our data. Variant chrM-15071-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 55

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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-CYB	ENST00000361789.2	TSL:6	c.325T>C	p.Tyr109His	missense	Exon 1 of 1	ENSP00000354554.2

Frequencies

Mitomap GenBank AF: 0.0018 AC: 108

Gnomad homoplasmic AF: 0.00097 AC: 55 AN: 56430

Gnomad heteroplasmic AF: 0.000071 AC: 4 AN: 56430

Alfa AF: 0.00136 Hom.: 69

Mitomap

No disease associated.

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Leigh syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.073
Hmtvar	Benign	0.26
AlphaMissense	Benign	0.079
PhyloP100		0.20
Mutation Taster		=90/10	polymorphism

Other links and lift over

dbSNP: rs199999794; hg19: chrM-15072;