chr12-57782803-TGTCGCTGCTGCG-T
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4
The NM_005726.6(TSFM):c.11_22delTGCGGTCGCTGC(p.Leu4_Leu7del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000044 in 1,590,470 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L4L) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000042 ( 0 hom. )
Consequence
TSFM
NM_005726.6 disruptive_inframe_deletion
NM_005726.6 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.01
Publications
1 publications found
Genes affected
TSFM (HGNC:12367): (Ts translation elongation factor, mitochondrial) This gene encodes a mitochondrial translation elongation factor. The encoded protein is an enzyme that catalyzes the exchange of guanine nucleotides on the translation elongation factor Tu during the elongation step of mitchondrial protein translation. Mutations in this gene are associated with combined oxidative phosphorylation deficiency-3 syndrome. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2010]
TSFM Gene-Disease associations (from GenCC):
- fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
- Leigh syndromeInheritance: AR Classification: MODERATE Submitted by: ClinGen
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_005726.6.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TSFM | NM_005726.6 | c.11_22delTGCGGTCGCTGC | p.Leu4_Leu7del | disruptive_inframe_deletion | Exon 1 of 6 | ENST00000652027.2 | NP_005717.3 | |
| TSFM | NM_001172696.2 | c.11_22delTGCGGTCGCTGC | p.Leu4_Leu7del | disruptive_inframe_deletion | Exon 1 of 7 | NP_001166167.1 | ||
| TSFM | NM_001172697.2 | c.11_22delTGCGGTCGCTGC | p.Leu4_Leu7del | disruptive_inframe_deletion | Exon 1 of 6 | NP_001166168.1 | ||
| TSFM | NM_001172695.2 | c.11_22delTGCGGTCGCTGC | p.Leu4_Leu7del | disruptive_inframe_deletion | Exon 1 of 5 | NP_001166166.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| TSFM | ENST00000652027.2 | c.11_22delTGCGGTCGCTGC | p.Leu4_Leu7del | disruptive_inframe_deletion | Exon 1 of 6 | NM_005726.6 | ENSP00000499171.2 | |||
| ENSG00000257921 | ENST00000546504.1 | c.77-298_77-287delTGCGGTCGCTGC | intron_variant | Intron 1 of 3 | 2 | ENSP00000449544.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152204
Hom.:
Cov.:
32
Gnomad AFR
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GnomAD2 exomes AF: 0.00 AC: 0AN: 213482 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
213482
AF XY:
Gnomad AFR exome
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GnomAD4 exome AF: 0.00000417 AC: 6AN: 1438266Hom.: 0 AF XY: 0.00000561 AC XY: 4AN XY: 713224 show subpopulations
GnomAD4 exome
AF:
AC:
6
AN:
1438266
Hom.:
AF XY:
AC XY:
4
AN XY:
713224
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32990
American (AMR)
AF:
AC:
0
AN:
41112
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25652
East Asian (EAS)
AF:
AC:
0
AN:
38250
South Asian (SAS)
AF:
AC:
1
AN:
82574
European-Finnish (FIN)
AF:
AC:
4
AN:
51164
Middle Eastern (MID)
AF:
AC:
0
AN:
5732
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1101322
Other (OTH)
AF:
AC:
0
AN:
59470
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
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0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74354 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152204
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74354
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41452
American (AMR)
AF:
AC:
0
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5194
South Asian (SAS)
AF:
AC:
0
AN:
4836
European-Finnish (FIN)
AF:
AC:
1
AN:
10622
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68036
Other (OTH)
AF:
AC:
0
AN:
2086
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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