rs35788393

Variant names:

• chrM-15904-C-T
• rs35788393
• unassigned_transcript_4819:c.17C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000000000(TRNT):​c.17C>T​(p.Thr6Ile) 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 Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.016 (AC: 999)
• Consequence: TRNT ENST00000000000 missense
• Scores: Mitotip Benign 1.7
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 Protective-factor-for-stroke-risk-(hg-V)
• Conservation: PhyloP100: -0.923
• Publications: 8 publications found

Genes affected

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

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]

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 -16 ACMG points.

• BP6: Variant M-15904-C-T is Benign according to our data. Variant chrM-15904-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 690224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: High frequency in mitomap database: 0.0163

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387460.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-TT	ENST00000387460.2	TSL:6	n.17C>T		non_coding_transcript_exon	Exon 1 of 1
	MT-CYB	ENST00000361789.2	TSL:6	c.*17C>T		downstream_gene	N/A	ENSP00000354554.2	P00156
	MT-TP	ENST00000387461.2	TSL:6	n.*52G>A		downstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.016 AC: 999

Gnomad homoplasmic AF: 0.022 AC: 1263 AN: 56425

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56425

Alfa AF: 0.0261 Hom.: 1204

Mitomap

Disease(s): Protective-factor-for-stroke-risk-(hg-V)

Status: Reported

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	MELAS syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	1.7
Hmtvar	Benign	0.20
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism

Other links and lift over

dbSNP: rs35788393; hg19: chrM-15905;