rs41504845

Variant names:

• chrM-15833-C-T
• rs41504845
• ENST00000361789.2:c.1087C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BS1 BS2

The ENST00000361789.2(MT-CYB):​c.1087C>T​(p.Leu363Leu) 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 0.0054 (AC: 332)
• Consequence: MT-CYB ENST00000361789.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.139
• 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]

TRNT (HGNC:7499): (mitochondrially encoded tRNA threonine)

TRNP (HGNC:7494): (mitochondrially encoded tRNA proline)

TRNP Gene-Disease associations (from GenCC):

• MERRF syndrome

  Inheritance: Mitochondrial Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP6: Variant M-15833-C-T is Benign according to our data. Variant chrM-15833-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 235581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.139 with no splicing effect.
• BS1: High frequency in mitomap database: 0.0054
• BS2: High AC in GnomadMitoHomoplasmic at 564

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTB	unassigned_transcript_4818	c.1087C>T	p.Leu363Leu	synonymous_variant	Exon 1 of 1
TRNT	unassigned_transcript_4819	c.-55C>T		upstream_gene_variant
TRNP	unassigned_transcript_4820	c.*123G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CYB	ENST00000361789.2	c.1087C>T	p.Leu363Leu	synonymous_variant	Exon 1 of 1	6		ENSP00000354554.2
MT-TT	ENST00000387460.2	n.-55C>T		upstream_gene_variant		6
MT-TP	ENST00000387461.2	n.*123G>A		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.0054 AC: 332

Gnomad homoplasmic AF: 0.010 AC: 564 AN: 56432

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56432

Alfa AF: 0.0125 Hom.: 701

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

May 26, 2015

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		-0.14

Other links and lift over

dbSNP: rs41504845; hg19: chrM-15834;