19-44899791-CTTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTT

Position:

• chr19-44899791-CTTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTT

Variant summary

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

The ENST00000426677.7(TOMM40):​c.644-909_644-904del 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 (0 hom., cov: 0)
• Consequence: TOMM40 ENST00000426677.7 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 nfe. gnomad4 allele frequency = 0.0104 (929/89702) while in subpopulation NFE AF= 0.0161 (708/44020). AF 95% confidence interval is 0.0151. There are 0 homozygotes in gnomad4. There are 386 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 929 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.644-909_644-904del		intron_variant		ENST00000426677.7	NP_001122389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.644-909_644-904del		intron_variant		1	NM_001128917.2	ENSP00000410339	P1

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

Gnomad4 AFR AF: 0.00182

Gnomad4 AMR AF: 0.00816

Gnomad4 ASJ AF: 0.0188

Gnomad4 EAS AF: 0.0111

Gnomad4 SAS AF: 0.00232

Gnomad4 FIN AF: 0.00586

Gnomad4 NFE AF: 0.0161

Gnomad4 OTH AF: 0.00491

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;