19-44899791-CTTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTT

Variant names:

• chr19-44899791-C-CT
• rs10524523
• NM_001128917.2:c.644-904dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001128917.2(TOMM40):​c.644-904dupT 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 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• 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: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1479 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.644-904dupT		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.644-939_644-938insT		intron_variant	Intron 5 of 8	1	NM_001128917.2	ENSP00000410339.1

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

African (AFR) AF: 0.00431 AC: 116 AN: 26914

American (AMR) AF: 0.0121 AC: 82 AN: 6772

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 111 AN: 2390

East Asian (EAS) AF: 0.00294 AC: 7 AN: 2382

South Asian (SAS) AF: 0.0129 AC: 28 AN: 2176

European-Finnish (FIN) AF: 0.00242 AC: 8 AN: 3306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 128

European-Non Finnish (NFE) AF: 0.0244 AC: 1094 AN: 44844

Other (OTH) AF: 0.0186 AC: 23 AN: 1236

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.0

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

Other links and lift over

dbSNP: rs10524523; hg19: chr19-45403048;