chr19-44899791-CTTTTTT-C

Variant names:

• chr19-44899791-CTTTTTT-C
• rs10524523
• NM_001128917.2:c.644-909_644-904delTTTTTT

Variant summary

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

The NM_001128917.2(TOMM40):​c.644-909_644-904delTTTTTT 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 0.010 (0 hom., cov: 0)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499
• Publications: 124 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.644-909_644-904delTTTTTT		intron_variant	Intron 5 of 8	ENST00000426677.7	NP_001122389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.644-938_644-933delTTTTTT		intron_variant	Intron 5 of 8	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 928 AN: 89694 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00183

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.00817

Gnomad ASJ AF: 0.0188

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.00231

Gnomad FIN AF: 0.00586

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0161

Gnomad OTH AF: 0.00412

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

GnomAD4 genome AF: 0.0104 AC: 929 AN: 89702 Hom.: 0 Cov.: 0 AF XY: 0.00938 AC XY: 386 AN XY: 41166

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

African (AFR) AF: 0.00182 AC: 49 AN: 26862

American (AMR) AF: 0.00816 AC: 55 AN: 6738

Ashkenazi Jewish (ASJ) AF: 0.0188 AC: 44 AN: 2338

East Asian (EAS) AF: 0.0111 AC: 26 AN: 2350

South Asian (SAS) AF: 0.00232 AC: 5 AN: 2158

European-Finnish (FIN) AF: 0.00586 AC: 19 AN: 3244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 124

European-Non Finnish (NFE) AF: 0.0161 AC: 708 AN: 44020

Other (OTH) AF: 0.00491 AC: 6 AN: 1222

⚠️ 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 v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism

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;