12-57782820-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_005726.6(TSFM):​c.19C>T​(p.Leu7Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L7L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TSFM
NM_005726.6 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.252

Publications

0 publications found
Variant links:
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 3
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
  • Leigh syndrome
    Inheritance: AR Classification: MODERATE Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 12-57782820-C-T is Benign according to our data. Variant chr12-57782820-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1653120.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.252 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TSFMNM_005726.6 linkc.19C>T p.Leu7Leu synonymous_variant Exon 1 of 6 ENST00000652027.2 NP_005717.3 P43897-1E5KS95
TSFMNM_001172696.2 linkc.19C>T p.Leu7Leu synonymous_variant Exon 1 of 7 NP_001166167.1 P43897-2
TSFMNM_001172697.2 linkc.19C>T p.Leu7Leu synonymous_variant Exon 1 of 6 NP_001166168.1 P43897-4
TSFMNM_001172695.2 linkc.19C>T p.Leu7Leu synonymous_variant Exon 1 of 5 NP_001166166.1 P43897-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TSFMENST00000652027.2 linkc.19C>T p.Leu7Leu synonymous_variant Exon 1 of 6 NM_005726.6 ENSP00000499171.2 P43897-1
ENSG00000257921ENST00000546504.1 linkc.77-290C>T intron_variant Intron 1 of 3 2 ENSP00000449544.1 H0YIJ7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.93e-7
AC:
1
AN:
1442236
Hom.:
0
Cov.:
30
AF XY:
0.00000140
AC XY:
1
AN XY:
715670
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33060
American (AMR)
AF:
0.00
AC:
0
AN:
41858
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25720
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38490
South Asian (SAS)
AF:
0.00
AC:
0
AN:
83034
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51318
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5738
European-Non Finnish (NFE)
AF:
9.06e-7
AC:
1
AN:
1103414
Other (OTH)
AF:
0.00
AC:
0
AN:
59604
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Sep 29, 2021
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
4.4
DANN
Benign
0.89
PhyloP100
-0.25
PromoterAI
0.010
Neutral

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs2140412505; hg19: chr12-58176603; API