chr19-44898512-T-TTTTTTTT

Variant names:

• chr19-44898511-C-CTTTTTTT
• rs34896370
• NM_001128917.2:c.644-2212_644-2206dupTTTTTTT

Variant summary

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

The NM_001128917.2(TOMM40):​c.644-2212_644-2206dupTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 1 publications found

Genes affected

TOMM40 (HGNC:18001): (translocase of outer mitochondrial membrane 40) The protein encoded by this gene is localized in the outer membrane of the mitochondria. It is the channel-forming subunit of the translocase of the mitochondrial outer membrane (TOM) complex that is essential for import of protein precursors into mitochondria. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128917.2. 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
	TOMM40	NM_001128917.2	MANE Select	c.644-2212_644-2206dupTTTTTTT		intron	N/A	NP_001122389.1	O96008-1
	TOMM40	NM_001128916.2		c.644-2212_644-2206dupTTTTTTT		intron	N/A	NP_001122388.1	O96008-1
	TOMM40	NM_006114.3		c.644-2212_644-2206dupTTTTTTT		intron	N/A	NP_006105.1	O96008-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOMM40	ENST00000426677.7	TSL:1 MANE Select	c.644-2219_644-2218insTTTTTTT		intron	N/A	ENSP00000410339.1	O96008-1
	TOMM40	ENST00000252487.9	TSL:1	c.644-2219_644-2218insTTTTTTT		intron	N/A	ENSP00000252487.4	O96008-1
	TOMM40	ENST00000405636.6	TSL:1	c.644-2219_644-2218insTTTTTTT		intron	N/A	ENSP00000385184.2	O96008-1

Frequencies

GnomAD3 genomes AF: 0.000294 AC: 29 AN: 98532 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000125

Gnomad AMI AF: 0.00272

Gnomad AMR AF: 0.000117

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000567

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000401

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000294 AC: 29 AN: 98532 Hom.: 0 Cov.: 0 AF XY: 0.000222 AC XY: 10 AN XY: 45092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000125 AC: 3 AN: 24030

American (AMR) AF: 0.000117 AC: 1 AN: 8548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2796

East Asian (EAS) AF: 0.000567 AC: 2 AN: 3530

South Asian (SAS) AF: 0.00 AC: 0 AN: 2844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 136

European-Non Finnish (NFE) AF: 0.000401 AC: 21 AN: 52360

Other (OTH) AF: 0.00 AC: 0 AN: 1336

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.8

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

dbSNP: rs34896370; hg19: chr19-45401768;