11-57528861-GAG-AAA

Variant names:

• chr11-57528861-GAG-AAA
• NM_012456.3:c.127_129delCTCinsTTT
• TIMM10 p.Leu43Phe

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_012456.3(TIMM10):​c.127_129delCTCinsTTT​(p.Leu43Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TIMM10 NM_012456.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.24
• Publications: 0 publications found

Genes affected

TIMM10 (HGNC:11814): (translocase of inner mitochondrial membrane 10) The mitochondrial protein encoded by this gene belongs to a family of evolutionarily conserved proteins that are organized in heterooligomeric complexes in the mitochondrial intermembrane space. These proteins mediate the import and insertion of hydrophobic membrane proteins into the mitochondrial inner membrane, functioning as intermembrane space chaperones for the highly insoluble carrier proteins. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012456.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMM10	NM_012456.3	MANE Select	c.127_129delCTCinsTTT	p.Leu43Phe	missense	N/A	NP_036588.1	P62072

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMM10	ENST00000257245.9	TSL:1 MANE Select	c.127_129delCTCinsTTT	p.Leu43Phe	missense	N/A	ENSP00000257245.4	P62072
	TIMM10	ENST00000525158.1	TSL:2	c.127_129delCTCinsTTT	p.Leu43Phe	missense	N/A	ENSP00000433627.1	P62072
	TIMM10	ENST00000525587.1	TSL:3	c.127_129delCTCinsTTT	p.Leu43Phe	missense	N/A	ENSP00000435678.1	P62072

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-57296334;