chr19-44899791-C-CT

Position:

• chr19-44899791-C-CT

Variant summary

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

The ENST00000426677.7(TOMM40):​c.644-904dup 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 0.016 (254 hom., cov: 0)
• Consequence: TOMM40 ENST00000426677.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01

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 = 0.0163 (1479/90798) while in subpopulation NFE AF= 0.0244 (1094/44844). AF 95% confidence interval is 0.0232. There are 254 homozygotes in gnomad4. There are 596 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1479 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 1478 AN: 90790 Hom.: 254 Cov.: 0

Gnomad AFR AF: 0.00428

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.00293

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.00242

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0244

Gnomad OTH AF: 0.0188

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

GnomAD4 genome AF: 0.0163 AC: 1479 AN: 90798 Hom.: 254 Cov.: 0 AF XY: 0.0143 AC XY: 596 AN XY: 41620

Gnomad4 AFR AF: 0.00431

Gnomad4 AMR AF: 0.0121

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.00294

Gnomad4 SAS AF: 0.0129

Gnomad4 FIN AF: 0.00242

Gnomad4 NFE AF: 0.0244

Gnomad4 OTH AF: 0.0186

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;