chr19-44898511-C-CTT

Variant names:

• chr19-44898511-C-CTT
• rs34896370
• NM_001128917.2:c.644-2207_644-2206dupTT

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 990 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.644-2207_644-2206dupTT		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.644-2219_644-2218insTT		intron_variant	Intron 5 of 8	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

African (AFR) AF: 0.0313 AC: 749 AN: 23936

American (AMR) AF: 0.0130 AC: 111 AN: 8528

Ashkenazi Jewish (ASJ) AF: 0.00322 AC: 9 AN: 2796

East Asian (EAS) AF: 0.00171 AC: 6 AN: 3514

South Asian (SAS) AF: 0.00354 AC: 10 AN: 2824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2216

Middle Eastern (MID) AF: 0.00794 AC: 1 AN: 126

European-Non Finnish (NFE) AF: 0.00168 AC: 88 AN: 52320

Other (OTH) AF: 0.0112 AC: 15 AN: 1342

Alfa AF: 0.00 Hom.: 259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs34896370; hg19: chr19-45401768;