3-119498922-CAA-C

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_016589.4(TIMMDC1):c.191_192del(p.Lys64ArgfsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TIMMDC1 NM_016589.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.61

Genes affected

TIMMDC1 (HGNC:1321): (translocase of inner mitochondrial membrane domain containing 1) Located in mitochondrion and nucleoplasm. Implicated in nuclear type mitochondrial complex I deficiency 31. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-119498922-CAA-C is Pathogenic according to our data. Variant chr3-119498922-CAA-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2498078.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIMMDC1	NM_016589.4	c.191_192del	p.Lys64ArgfsTer2	frameshift_variant	1/7	ENST00000494664.6
TIMMDC1	XM_017006556.2	c.191_192del	p.Lys64ArgfsTer17	frameshift_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIMMDC1	ENST00000494664.6	c.191_192del	p.Lys64ArgfsTer2	frameshift_variant	1/7	1	NM_016589.4	P1

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

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mitochondrial complex I deficiency, nuclear type 1 Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Payam Genetics Center, General Welfare Department of North Khorasan Province

Mar 01, 2023

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.21		Position offset: 5

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: chr3-119217769;