rs41456348

Positions:

• chrM-4336-T-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The ENST00000387372.1(MT-TQ):​n.65A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency: Mitomap GenBank: 𝑓 0.0088 (AC: 535)
• Consequence: MT-TQ ENST00000387372.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 11
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1 U:1 B:2 ADPD-/-Hearing-Loss-&-Migraine-/-autism-spectrum-/-intellectual-disability
• Conservation: PhyloP100: -1.81

Genes affected

MT-TQ (HGNC:7495): (mitochondrially encoded tRNA glutamine)

TRNQ (HGNC:):

MT-TI (HGNC:7488): (mitochondrially encoded tRNA isoleucine)

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant M-4336-T-C is Benign according to our data. Variant chrM-4336-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 9615.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=1}.
• BS1: High frequency in mitomap database: 0.0088
• BS2: High AC in GnomadMitoHomoplasmic at 737

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNQ	TRNQ.1	n.65A>G		non_coding_transcript_exon_variant	1/1
TRNI	TRNI.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TQ	ENST00000387372.1	n.65A>G		non_coding_transcript_exon_variant	1/1
MT-TI	ENST00000387365.1			downstream_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: 0.0088 AC: 535

Gnomad homoplasmic AF: 0.013 AC: 737 AN: 56424

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56424

Alfa AF: 0.0207 Hom.: 1487

Mitomap

ADPD-/-Hearing-Loss-&-Migraine-/-autism-spectrum-/-intellectual-disability

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1 Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Sensorineural deafness and migraine Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2001

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

May 26, 2015

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Aug 17, 2020

- -

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.4336T>C variant in MT-TQ 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, BS4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	11
Hmtvar	Pathogenic	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41456348; hg19: chrM-4337;