Variant rs111033319 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP6_Strong

Variant has been reported in ClinVar as Uncertain significance (★★★).

Frequency

Mitomap GenBank:

𝑓 0.00050 ( AC: 30 )

Consequence

TRNS1
frameshift

Scores

Mitotip

Uncertain

Clinical Significance

Uncertain significance reviewed by expert panel U:2B:1

Maternally-inherited-hypertension-/-deafness

Conservation

PhyloP100: 3.93

Variant links:

Genes affected

TRNS1 (HGNC:):

TRNS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP6

Variant M-7465-AC-A is Benign according to our data. Variant chrM-7465-AC-A is described in ClinVar as [Uncertain_significance]. Clinvar id is 42227.Status of the report is reviewed_by_expert_panel, 3 stars. We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
TRNS1	unassigned_transcript_4801 use as main transcript	c.49delG	p.Val17fs	frameshift_variant	1/1
COX1	unassigned_transcript_4800 use as main transcript	c.*21delC		downstream_gene_variant
	use as main transcript

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome

Cov.:

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

Mitomap GenBank

AF:

0.00050

AC:

Alfa

AF:

0.000786

Hom.:

Mitomap

Maternally-inherited-hypertension-/-deafness

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2Benign:1

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 03, 2011

The 7471delC variant in MTTS1 has not been reported in the literature nor previo usly identified by our laboratory. However, this deletion of a cytosine (C) nucl eotide occurs within a stretch of 6 cytosine nucleotides and a similar variant ( 7471_7472insC) resulting in an insertion of a cytosine in this same stretch of c ytosine residues has been previously reported in individuals with both nonsyndro mic and syndromic hearing loss (Tiranti 1995, Ensink 1998, Jaksch 1998, Verhoeve n 1999, Hutchin 2001). However, the 7471delC may have a different affect than th e 7471_7472insC variant on the MTTS1 gene. In summary, the clinical significance of this variant cannot be determined with certainty at this time. -

Mitochondrial disease

Uncertain:1

Uncertain significance, reviewed by expert panel

curation

ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen

May 22, 2023

The m.7471delC variant in MT-TS1 was reviewed by the Mitochondrial Disease Variant Curation Expert Panel on May 22, 2023. This variant has not been reported in the medical literature as causative in affected individuals or families with primary mitochondrial disease to our knowledge. This variant is present in population databases (Mitomap's 28/59,389 sequences: AF= 0.047%; Helix's 162/195,983 sequences: AF=0.070% including 137 homoplasmic occurrences in addition to 25 heteroplasmic occurrences, and in haplogroups H, U, T, K, B, D, M, HV, J, A, I, X, T, C, K, M, W, V; and gnomAD v3.1.2: AF=0.053 % including 30 homoplasmic occurrences in addition to five heteroplasmic occurrences). Given the frequency of this variant, it does not meet PM2 criterion. The computational predictor MitoTIP suggests this variant is benign (4.3 percentile) and HmtVAR does not provide a prediction. Given the lack of computational evidence, BP4 cannot be applied. There are no cybrids, single fiber studies, or other functional assays reported on this variant. In summary, this variant meets criteria to be classified as uncertain significance for primary mitochondrial disease inherited in a mitochondrial manner. We note that three experts on this panel felt likely benign was a more appropriate classification given the presence in the general population however the majority (four) agreed with uncertain significance. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Variant Curation Expert Panel on May 22, 2023. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): None. -

MELAS syndrome

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.7471delC variant in MT-TS1 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