rs397507452

Positions:

• chrM-7443-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 1)
• Consequence: COX1 missense, splice_region
• Clinical Significance: Pathogenic criteria provided, single submitter P:1 O:1 DEAF
• Conservation: PhyloP100: -0.146

Genes affected

COX1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• PP5: Variant M-7443-A-G is Pathogenic according to our data. Variant chrM-7443-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 40158.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX1	unassigned_transcript_4800	c.1540A>G	p.Arg514Gly	missense_variant, splice_region_variant	1/1
TRNS1	unassigned_transcript_4801	c.*3T>C		downstream_gene_variant

Ensembl

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

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.0 AC: 1

Gnomad homoplasmic AF: 0.000018 AC: 1 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Mitomap

DEAF

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mitochondrial non-syndromic sensorineural hearing loss Pathogenic:1 Other:1

not provided, no classification provided	literature only	GeneReviews	-	- -
Pathogenic, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.49	T
GERP RS		2.4
Varity_R		0.17

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs397507452; hg19: chrM-7444;