chr19-44892587-G-A

Variant names:

• chr19-44892587-G-A
• rs34095326
• NM_001128917.2:c.342+127G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128917.2(TOMM40):​c.342+127G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0895 in 924,960 control chromosomes in the GnomAD database, including 4,724 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 0.075 (625 hom., cov: 32)
  • Exomes 𝑓: 0.092 (4099 hom.)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.660
• Publications: 36 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.342+127G>A		intron_variant	Intron 2 of 8	ENST00000426677.7	NP_001122389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.342+127G>A		intron_variant	Intron 2 of 8	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.0754 AC: 11474 AN: 152094 Hom.: 626 Cov.: 32

Gnomad AFR AF: 0.0192

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0454

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0279

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0507

GnomAD4 exome AF: 0.0923 AC: 71326 AN: 772748 Hom.: 4099 AF XY: 0.0909 AC XY: 36604 AN XY: 402570

African (AFR) AF: 0.0155 AC: 300 AN: 19364

American (AMR) AF: 0.0300 AC: 1021 AN: 34024

Ashkenazi Jewish (ASJ) AF: 0.0932 AC: 1803 AN: 19350

East Asian (EAS) AF: 0.000146 AC: 5 AN: 34172

South Asian (SAS) AF: 0.0315 AC: 2034 AN: 64486

European-Finnish (FIN) AF: 0.160 AC: 7793 AN: 48830

Middle Eastern (MID) AF: 0.0281 AC: 78 AN: 2776

European-Non Finnish (NFE) AF: 0.108 AC: 55313 AN: 512432

Other (OTH) AF: 0.0798 AC: 2979 AN: 37314

GnomAD4 genome AF: 0.0754 AC: 11471 AN: 152212 Hom.: 625 Cov.: 32 AF XY: 0.0771 AC XY: 5737 AN XY: 74404

African (AFR) AF: 0.0192 AC: 796 AN: 41538

American (AMR) AF: 0.0454 AC: 694 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 361 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.0282 AC: 136 AN: 4828

European-Finnish (FIN) AF: 0.161 AC: 1701 AN: 10586

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7550 AN: 68004

Other (OTH) AF: 0.0502 AC: 106 AN: 2112

Alfa AF: 0.0867 Hom.: 782

Bravo AF: 0.0632

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.6
DANN	Benign	0.75
PhyloP100		0.66
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: rs34095326; hg19: chr19-45395844;