chr7-22822693-AG-CA

Variant names:

• chr7-22822693-AG-CA
• NM_019059.5:c.86_87delCTinsTG
• TOMM7 p.Pro29Leu

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PS1 PP2 PP3

The NM_019059.5(TOMM7):​c.86_87delCTinsTG​(p.Pro29Leu) 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 Pathogenic in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TOMM7 NM_019059.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.67
• Publications: 0 publications found

Genes affected

TOMM7 (HGNC:21648): (translocase of outer mitochondrial membrane 7) This gene encodes a subunit of the translocase of the outer mitochondrial membrane. The encoded protein regulates the assembly and stability of the translocase complex. [provided by RefSeq, Oct 2012]

TOMM7 Gene-Disease associations (from GenCC):

• Garg-Mishra progeroid syndrome

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics

ENSG00000286703 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PS1: Transcript NM_019059.5 (TOMM7) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 2 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: -0.15261 (below the threshold of 3.09). Trascript score misZ: -0.33228 (below the threshold of 3.09). GenCC associations: The gene is linked to Garg-Mishra progeroid syndrome.
• 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_019059.5. 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
	TOMM7	NM_019059.5	MANE Select	c.86_87delCTinsTG	p.Pro29Leu	missense	N/A	NP_061932.1	Q9P0U1
	TOMM7	NR_168014.1		n.129+27_129+28delCTinsTG		intron	N/A
	TOMM7	NR_168015.1		n.129+27_129+28delCTinsTG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOMM7	ENST00000358435.9	TSL:1 MANE Select	c.86_87delCTinsTG	p.Pro29Leu	missense	N/A	ENSP00000351214.4	Q9P0U1
	TOMM7	ENST00000496129.1	TSL:1	n.117_118delCTinsTG		non_coding_transcript_exon	Exon 1 of 2
	TOMM7	ENST00000372879.8	TSL:4	c.86_87delCTinsTG	p.Pro29Leu	missense	N/A	ENSP00000361970.4	A6NIV2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.7

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: chr7-22862312;