M-15487-A-T

Variant names:

• chrM-15487-A-T
• rs28357370
• ENST00000361789.2:c.741A>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP7 BA1

The ENST00000361789.2(MT-CYB):​c.741A>T​(p.Pro247Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P247P) has been classified as Likely benign.

• Frequency: Mitomap GenBank: 𝑓 0.042 (AC: 2559)
• Consequence: MT-CYB ENST00000361789.2 synonymous
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: -6.76
• 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 -9 ACMG points.

• BP7: Synonymous conserved (PhyloP=-6.76 with no splicing effect.
• BA1: High frequency in mitomap database: 0.0419

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTB	unassigned_transcript_4818	c.741A>T	p.Pro247Pro	synonymous_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CYB	ENST00000361789.2	c.741A>T	p.Pro247Pro	synonymous_variant	Exon 1 of 1	6		ENSP00000354554.2

Frequencies

Mitomap GenBank AF: 0.042 AC: 2559

Gnomad homoplasmic AF: 0.018 AC: 1010 AN: 56427

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56427

Alfa AF: 0.00485 Hom.: 180

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-6.8
Mutation Taster		=77/23	polymorphism

Other links and lift over

dbSNP: rs28357370; hg19: chrM-15488;