19-44899791-CTTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTT

Position:

• chr19-44899791-CTTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTT

Variant summary

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

The NM_001128917.2(TOMM40):​c.644-916_644-904delTTTTTTTTTTTTT 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 0.020 (6 hom., cov: 0)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499

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 = 0.0203 (1835/90588) while in subpopulation AFR AF= 0.0283 (758/26788). AF 95% confidence interval is 0.0266. There are 6 homozygotes in gnomad4. There are 827 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1835 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.644-916_644-904delTTTTTTTTTTTTT		intron_variant		ENST00000426677.7	NP_001122389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.644-916_644-904delTTTTTTTTTTTTT		intron_variant		1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 1834 AN: 90578 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.00154

Gnomad AMR AF: 0.00945

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.00209

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.00725

Gnomad NFE AF: 0.0190

Gnomad OTH AF: 0.0163

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

GnomAD4 genome AF: 0.0203 AC: 1835 AN: 90588 Hom.: 6 Cov.: 0 AF XY: 0.0199 AC XY: 827 AN XY: 41572

Gnomad4 AFR AF: 0.0283

Gnomad4 AMR AF: 0.00929

Gnomad4 ASJ AF: 0.0280

Gnomad4 EAS AF: 0.00209

Gnomad4 SAS AF: 0.0143

Gnomad4 FIN AF: 0.0121

Gnomad4 NFE AF: 0.0190

Gnomad4 OTH AF: 0.0162

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: rs10524523; hg19: chr19-45403048;