M-591-C-T

Position:

• chrM-591-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 10P and 1B. PM2 PP5_Very_Strong BP4

The ENST00000387314.1(MT-TF):​n.15C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely pathogenic (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: MT-TF ENST00000387314.1 non_coding_transcript_exon
• Scores: Mitotip Benign 3.2
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:2 Gitelman-like-syndrome
• Conservation: PhyloP100: 0.341

Genes affected

MT-TF (HGNC:7481): (mitochondrially encoded tRNA phenylalanine)

TRNF (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• PP5: Variant M-591-C-T is Pathogenic according to our data. Variant chrM-591-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1177637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP4: Mitotip and hmtvar scores support benign criterium.. Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNF	TRNF.1	n.15C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TF	ENST00000387314.1	n.15C>T		non_coding_transcript_exon_variant	1/1

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: 0

Gnomad homoplasmic AF: 0.0 AC: 0 AN: 56432

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56432

Mitomap

Gitelman-like-syndrome

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Nephropathy, chronic tubulointerstitial Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Undiagnosed Diseases Network, NIH

Jul 22, 2022

- -

Hypokalemia;C0151723:Hypomagnesemia Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Jul 02, 2021

The m.591C>T variant was observed in 7 families affected by hypomagnesemia with renal magnesium wasting and hypokalemia.(Viering et al. 2021) The variant segregated with disease in 20 individuals in these 7 families. Several patients additionally suffered from reduced glomerular filtration. The variant was scored as pathogenic when using the system published by Wong et al. (2020) as basis: PS2, PS4, PM9, PM10, PP6, PP7, BP4. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	3.2
Hmtvar	Benign	0.0

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrM-593;