rs3134560

chrM-12192-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000387441.1(MT-TH):n.55G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0021 (AC: 126)
• Consequence: MT-TH ENST00000387441.1 non_coding_transcript_exon
• Scores: Mitotip Benign 2.7
• Clinical Significance: Benign criteria provided, single submitter P:2 B:1 MICM-/-possible-G15927A-deafness-modulator
• Conservation: PhyloP100: -4.60

Genes affected

MT-TH (HGNC:7487): (mitochondrially encoded tRNA histidine)

TRNH (HGNC:):

MT-TS2 (HGNC:7498): (mitochondrially encoded tRNA serine 2 (AGU/C))

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Mitotip and hmtvar scores support benign criterium.
• BP6: Variant M-12192-G-A is Benign according to our data. Variant chrM-12192-G-A is described in ClinVar as [Benign]. Clinvar id is 9608.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 223

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNH	TRNH.1	n.55G>A		non_coding_transcript_exon_variant	1/1
TRNS2	TRNS2.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TH	ENST00000387441.1	n.55G>A		non_coding_transcript_exon_variant	1/1
MT-TS2	ENST00000387449.1			upstream_gene_variant

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap GenBank AF: 0.0021 AC: 126

Gnomad homoplasmic AF: 0.0040 AC: 223 AN: 56428

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56428

Mitomap

MICM-/-possible-G15927A-deafness-modulator

ClinVar

Significance: Benign

Submissions summary: Pathogenic:2 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cardiomyopathy, hypertrophic, mitochondrial Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 2003

- -

Cardiomyopathy, idiopathic dilated, mitochondrial Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 2003

- -

Juvenile myopathy, encephalopathy, lactic acidosis AND stroke Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Jul 12, 2019

The NC_012920.1:m.12192G>A variant in MT-TH 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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	2.7
Hmtvar	Benign	0.20

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3134560; hg19: chrM-12193;