19-44899959-C-T

Position:

• chr19-44899959-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001128917.2(TOMM40):​c.644-771C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 151,838 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.028 (62 hom., cov: 30)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0281 (4274/151838) while in subpopulation AFR AF= 0.0427 (1770/41426). AF 95% confidence interval is 0.0411. There are 62 homozygotes in gnomad4. There are 2062 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4274 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOMM40	NM_001128917.2	c.644-771C>T		intron_variant		ENST00000426677.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOMM40	ENST00000426677.7	c.644-771C>T		intron_variant		1	NM_001128917.2	P1

Frequencies

GnomAD3 genomes AF: 0.0281 AC: 4268 AN: 151722 Hom.: 60 Cov.: 30

Gnomad AFR AF: 0.0426

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.0309

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0246

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.0197

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

GnomAD4 genome AF: 0.0281 AC: 4274 AN: 151838 Hom.: 62 Cov.: 30 AF XY: 0.0278 AC XY: 2062 AN XY: 74220

Gnomad4 AFR AF: 0.0427

Gnomad4 AMR AF: 0.0123

Gnomad4 ASJ AF: 0.0309

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.0244

Gnomad4 FIN AF: 0.0238

Gnomad4 NFE AF: 0.0263

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0291 Hom.: 17

Bravo AF: 0.0285

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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

Publications

LitVar

Other links and lift over

dbSNP: rs115881343; hg19: chr19-45403216;