NM_005726.6:c.6G>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_005726.6(TSFM):​c.6G>T​(p.Ser2Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,439,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TSFM
NM_005726.6 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP7
Synonymous conserved (PhyloP=1.07 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TSFMNM_005726.6 linkc.6G>T p.Ser2Ser synonymous_variant Exon 1 of 6 ENST00000652027.2 NP_005717.3 P43897-1E5KS95
TSFMNM_001172696.2 linkc.6G>T p.Ser2Ser synonymous_variant Exon 1 of 7 NP_001166167.1 P43897-2
TSFMNM_001172697.2 linkc.6G>T p.Ser2Ser synonymous_variant Exon 1 of 6 NP_001166168.1 P43897-4
TSFMNM_001172695.2 linkc.6G>T p.Ser2Ser 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.6G>T p.Ser2Ser synonymous_variant Exon 1 of 6 NM_005726.6 ENSP00000499171.2 P43897-1
ENSG00000257921ENST00000546504.1 linkc.77-303G>T intron_variant Intron 1 of 3 2 ENSP00000449544.1 H0YIJ7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000139
AC:
2
AN:
1439194
Hom.:
0
Cov.:
30
AF XY:
0.00000280
AC XY:
2
AN XY:
713764
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000182
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
CADD
Benign
8.0
DANN
Benign
0.71
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: chr12-58176590; API