rs199474818

Positions:

• chrM-7445-A-C
• chrM-7445-A-G
• chrM-7445-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP5_Moderate

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

• Frequency: Mitomap GenBank: 𝑓 0.00030 (AC: 17)
• Consequence: COX1 missense, splice_region
• Clinical Significance: Pathogenic criteria provided, single submitter P:2 O:1 DEAF,SNHL,SNHL
• Conservation: PhyloP100: -0.943

Genes affected

COX1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PP5: Variant M-7445-A-C is Pathogenic according to our data. Variant chrM-7445-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 9568.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.1542A>C	p.Arg514Ser	missense_variant, splice_region_variant	1/1
TRNS1	unassigned_transcript_4801	c.*1T>G		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: 0.00030 AC: 17

Mitomap

DEAF,SNHL,SNHL

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mitochondrial non-syndromic sensorineural hearing loss Pathogenic:2 Other:1

Pathogenic, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -
not provided, no classification provided	literature only	GeneReviews	-	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Sep 14, 2007	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.33	T
GERP RS		-0.79
Varity_R		0.24

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs199474818; hg19: chrM-7446;