19-44898511-CTT-CTTTT

Position:

• chr19-44898511-CTT-CTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001128917.2(TOMM40):​c.644-2207_644-2206dupTT 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 0.010 (8 hom., cov: 0)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

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

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (990/98338) while in subpopulation AFR AF= 0.0313 (749/23936). AF 95% confidence interval is 0.0294. There are 8 homozygotes in gnomad4. There are 502 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 990 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.644-2207_644-2206dupTT		intron_variant		ENST00000426677.7	NP_001122389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.644-2207_644-2206dupTT		intron_variant		1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 990 AN: 98354 Hom.: 8 Cov.: 0

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.00136

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.00322

Gnomad EAS AF: 0.00170

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00735

Gnomad NFE AF: 0.00168

Gnomad OTH AF: 0.0113

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

GnomAD4 genome AF: 0.0101 AC: 990 AN: 98338 Hom.: 8 Cov.: 0 AF XY: 0.0111 AC XY: 502 AN XY: 45026

Gnomad4 AFR AF: 0.0313

Gnomad4 AMR AF: 0.0130

Gnomad4 ASJ AF: 0.00322

Gnomad4 EAS AF: 0.00171

Gnomad4 SAS AF: 0.00354

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00168

Gnomad4 OTH AF: 0.0112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34896370; hg19: chr19-45401768;