chr19-44899791-CTTTTT-C

Variant names:

• chr19-44899791-CTTTTT-C
• rs10524523
• NM_001128917.2:c.644-908_644-904delTTTTT

Variant summary

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

The NM_001128917.2(TOMM40):​c.644-908_644-904delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0011 (0 hom., cov: 0)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280
• Publications: 125 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.644-908_644-904delTTTTT		intron	N/A	NP_001122389.1	O96008-1
	TOMM40	NM_001128916.2		c.644-908_644-904delTTTTT		intron	N/A	NP_001122388.1	O96008-1
	TOMM40	NM_006114.3		c.644-908_644-904delTTTTT		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.644-938_644-934delTTTTT		intron	N/A	ENSP00000410339.1	O96008-1
	TOMM40	ENST00000252487.9	TSL:1	c.644-938_644-934delTTTTT		intron	N/A	ENSP00000252487.4	O96008-1
	TOMM40	ENST00000405636.6	TSL:1	c.644-938_644-934delTTTTT		intron	N/A	ENSP00000385184.2	O96008-1

Frequencies

GnomAD3 genomes AF: 0.00106 AC: 96 AN: 90802 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00326

Gnomad ASJ AF: 0.00125

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000458

Gnomad FIN AF: 0.000605

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.00163

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

GnomAD4 genome AF: 0.00106 AC: 96 AN: 90810 Hom.: 0 Cov.: 0 AF XY: 0.000865 AC XY: 36 AN XY: 41636

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

African (AFR) AF: 0.000223 AC: 6 AN: 26930

American (AMR) AF: 0.00326 AC: 22 AN: 6756

Ashkenazi Jewish (ASJ) AF: 0.00125 AC: 3 AN: 2398

East Asian (EAS) AF: 0.00 AC: 0 AN: 2394

South Asian (SAS) AF: 0.000460 AC: 1 AN: 2174

European-Finnish (FIN) AF: 0.000605 AC: 2 AN: 3308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 128

European-Non Finnish (NFE) AF: 0.00134 AC: 60 AN: 44836

Other (OTH) AF: 0.00162 AC: 2 AN: 1236

⚠️ 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.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.28

Splicing

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

Other links and lift over

dbSNP: rs10524523; hg19: chr19-45403048;