M-15191-T-C

Variant names:

• chrM-15191-T-C
• rs878912989
• ENST00000361789.2:c.445T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP6_Moderate BP7 BS2

The ENST00000361789.2(MT-CYB):​c.445T>C​(p.Leu149Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0016 (AC: 95)
• Consequence: MT-CYB ENST00000361789.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.381
• Publications: 4 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 -7 ACMG points.

• BP6: Variant M-15191-T-C is Benign according to our data. Variant chrM-15191-T-C is described in CliVar as Likely_benign. Clinvar id is 445359.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrM-15191-T-C is described in CliVar as Likely_benign. Clinvar id is 445359.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrM-15191-T-C is described in CliVar as Likely_benign. Clinvar id is 445359.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.381 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 116

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTB	unassigned_transcript_4818	c.445T>C	p.Leu149Leu	synonymous_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CYB	ENST00000361789.2	c.445T>C	p.Leu149Leu	synonymous_variant	Exon 1 of 1	6		ENSP00000354554.2

Frequencies

Mitomap GenBank AF: 0.0016 AC: 95

Gnomad homoplasmic AF: 0.0021 AC: 116 AN: 56428

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56428

Alfa AF: 0.00122 Hom.: 5

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 07, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38
Mutation Taster		=33/67	disease causing

Other links and lift over

dbSNP: rs878912989; hg19: chrM-15192; COSMIC: COSV62377814; COSMIC: COSV62377814;