rs199474700

Variant names:

• chrM-15965-A-G
• rs199474700
• unassigned_transcript_4820:c.59T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000000000(TRNP):​c.59T>C​(p.Phe20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 3/3 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00020 (AC: 12)
• Consequence: TRNP ENST00000000000 missense
• Scores: Mitotip Benign 1.9
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1 Dopaminergic-nerve-cell-death-(PD)
• Conservation: PhyloP100: 0.985
• Publications: 2 publications found

Genes affected

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

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)

TRNT Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant M-15965-A-G is Benign according to our data. Variant chrM-15965-A-G is described in ClinVar as Benign. ClinVar VariationId is 9571.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 17

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNP	unassigned_transcript_4820	c.59T>C	p.Phe20Ser	missense_variant	Exon 1 of 1
CYTB	unassigned_transcript_4818	c.*78A>G		downstream_gene_variant
TRNT	unassigned_transcript_4819	c.*12A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-TP	ENST00000387461.2	n.59T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-CYB	ENST00000361789.2	c.*78A>G		downstream_gene_variant		6		ENSP00000354554.2
MT-TT	ENST00000387460.2	n.*12A>G		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.00020 AC: 12

Gnomad homoplasmic AF: 0.00030 AC: 17 AN: 56433

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56433

Alfa AF: 0.000327 Hom.: 6

Mitomap

Disease(s): Dopaminergic-nerve-cell-death-(PD)

Status: Reported

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

MELAS syndrome Benign:1

Jul 12, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.15965A>G variant in MT-TP gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS2, BP4 -

Parkinson disease, mitochondrial Other:1

Apr 01, 1999

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	1.9
Hmtvar	Benign	0.20
PhyloP100		0.98

Other links and lift over

dbSNP: rs199474700; hg19: chrM-15966;