NM_001001563.5:c.25_27delTCGinsCTC

Variant names:

• chr19-39480878-TCG-CTC
• NM_001001563.5:c.25_27delTCGinsCTC
• TIMM50 p.Ser9Leu

Variant summary

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

The NM_001001563.5(TIMM50):​c.25_27delTCGinsCTC​(p.Ser9Leu) variant causes a missense change involving the alteration of a non-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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S9W) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: TIMM50 NM_001001563.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413
• Publications: 0 publications found

Genes affected

TIMM50 (HGNC:23656): (translocase of inner mitochondrial membrane 50) This gene encodes a subunit of the TIM23 inner mitochondrial membrane translocase complex. The encoded protein functions as the receptor subunit that recognizes the mitochondrial targeting signal, or presequence, on protein cargo that is destined for the mitochondrial inner membrane and matrix. This protein may also play a role in maintaining the membrane permeability barrier, and knockdown of this gene in human cells results in the release of cytochrome c and apoptosis. [provided by RefSeq, Jul 2016]

TIMM50 Gene-Disease associations (from GenCC):

• 3-methylglutaconic aciduria type 9

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001563.5. 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
	TIMM50	NM_001001563.5	MANE Select	c.25_27delTCGinsCTC	p.Ser9Leu	missense	N/A	NP_001001563.2	Q3ZCQ8-1
	TIMM50	NM_001329559.2		c.-256_-254delTCGinsCTC		5_prime_UTR	Exon 1 of 10	NP_001316488.1	Q3ZCQ8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMM50	ENST00000607714.6	TSL:1 MANE Select	c.25_27delTCGinsCTC	p.Ser9Leu	missense	N/A	ENSP00000475531.1	Q3ZCQ8-1
	TIMM50	ENST00000544017.5	TSL:1	c.334_336delTCGinsCTC	p.Ser112Leu	missense	N/A	ENSP00000445806.2	Q3ZCQ8-2
	TIMM50	ENST00000601358.5	TSL:1	n.25_27delTCGinsCTC		non_coding_transcript_exon	Exon 1 of 10	ENSP00000472476.2	M0R2D2

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.41

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: chr19-39971518;