19-44898526-T-C

Position:

• chr19-44898526-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001128917.2(TOMM40):​c.644-2204T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.37 (3087 hom., cov: 13)
  • Failed GnomAD Quality Control
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOMM40	NM_001128917.2	c.644-2204T>C		intron_variant		ENST00000426677.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOMM40	ENST00000426677.7	c.644-2204T>C		intron_variant		1	NM_001128917.2	P1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 32248 AN: 86288 Hom.: 3088 Cov.: 13

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.345

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.374 AC: 32253 AN: 86294 Hom.: 3087 Cov.: 13 AF XY: 0.370 AC XY: 14566 AN XY: 39342

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.345

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.46

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: rs56290633; hg19: chr19-45401783;