Genetic Variant TOMM20L:p.Glu89Gly (chr14-58407329-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207377.3(TOMM20L):c.266A>G(p.Glu89Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,302 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TOMM20L
NM_207377.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.61

Variant links:

Genes affected

TOMM20L (HGNC:33752): (translocase of outer mitochondrial membrane 20 like) Predicted to enable mitochondrion targeting sequence binding activity. Predicted to contribute to protein transmembrane transporter activity. Predicted to be involved in protein import into mitochondrial matrix and tRNA import into mitochondrion. Predicted to be integral component of membrane. Predicted to be part of mitochondrial outer membrane translocase complex. Predicted to be integral component of mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

TOMM20L links:

ENSG00000258378 (HGNC:):

ENSG00000258378 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21359009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM20L	NM_207377.3 link	c.266A>G	p.Glu89Gly	missense_variant	Exon 4 of 5	ENST00000360945.7	NP_997260.1	Q6UXN7
TOMM20L	XM_011536742.4 link	c.290A>G	p.Glu97Gly	missense_variant	Exon 4 of 5		XP_011535044.1
TOMM20L	XM_011536743.3 link	c.290A>G	p.Glu97Gly	missense_variant	Exon 4 of 5		XP_011535045.1
TOMM20L	XM_011536744.4 link	c.140A>G	p.Glu47Gly	missense_variant	Exon 2 of 3		XP_011535046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TOMM20L	ENST00000360945.7 link	c.266A>G	p.Glu89Gly	missense_variant	Exon 4 of 5	1	NM_207377.3	ENSP00000354204.2	Q6UXN7
TOMM20L	ENST00000557754.1 link	n.184A>G		non_coding_transcript_exon_variant	Exon 3 of 4	1		ENSP00000451683.1	G3V4A4
ENSG00000258378	ENST00000556734.1 link	n.374+8399A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000425

AC:

AN:

235264

Hom.:

AF XY:

0.00

AC XY:

AN XY:

127534

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000922

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1447098

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719786

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Benign

0.59

DEOGEN2

Benign

0.064

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.51

M_CAP

Benign

0.013

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.6

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.16

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.060

Polyphen

0.98

Vest4

0.26

MutPred

0.42

Gain of MoRF binding (P = 0.0267);

MVP

0.16

MPC

1.3

ClinPred

0.98

GERP RS

4.8

Varity_R

0.68

gMVP

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over