19-44898526-T-C

Variant names:

• chr19-44898526-T-C
• rs56290633
• NM_001128917.2:c.644-2204T>C

Variant summary

Our verdict is Likely benign. The variant received -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
• 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: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128917.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOMM40	NM_001128917.2	MANE Select	c.644-2204T>C		intron	N/A	NP_001122389.1	O96008-1
	TOMM40	NM_001128916.2		c.644-2204T>C		intron	N/A	NP_001122388.1	O96008-1
	TOMM40	NM_006114.3		c.644-2204T>C		intron	N/A	NP_006105.1	O96008-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOMM40	ENST00000426677.7	TSL:1 MANE Select	c.644-2204T>C		intron	N/A	ENSP00000410339.1	O96008-1
	TOMM40	ENST00000252487.9	TSL:1	c.644-2204T>C		intron	N/A	ENSP00000252487.4	O96008-1
	TOMM40	ENST00000405636.6	TSL:1	c.644-2204T>C		intron	N/A	ENSP00000385184.2	O96008-1

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

African (AFR) AF: 0.417 AC: 8315 AN: 19962

American (AMR) AF: 0.347 AC: 2528 AN: 7282

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1011 AN: 2620

East Asian (EAS) AF: 0.206 AC: 651 AN: 3164

South Asian (SAS) AF: 0.283 AC: 730 AN: 2584

European-Finnish (FIN) AF: 0.351 AC: 639 AN: 1820

Middle Eastern (MID) AF: 0.250 AC: 37 AN: 148

European-Non Finnish (NFE) AF: 0.376 AC: 17643 AN: 46932

Other (OTH) AF: 0.345 AC: 402 AN: 1164

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.46
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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: rs56290633; hg19: chr19-45401783;