rs367612244

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_207377.3(TOMM20L):c.266A>C(p.Glu89Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000563 in 1,599,400 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

TOMM20L
NM_207377.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

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=0.24114203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM20L	NM_207377.3 link	c.266A>C	p.Glu89Ala	missense_variant	Exon 4 of 5	ENST00000360945.7	NP_997260.1	Q6UXN7
TOMM20L	XM_011536742.4 link	c.290A>C	p.Glu97Ala	missense_variant	Exon 4 of 5		XP_011535044.1
TOMM20L	XM_011536743.3 link	c.290A>C	p.Glu97Ala	missense_variant	Exon 4 of 5		XP_011535045.1
TOMM20L	XM_011536744.4 link	c.140A>C	p.Glu47Ala	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>C	p.Glu89Ala	missense_variant	Exon 4 of 5	1	NM_207377.3	ENSP00000354204.2	Q6UXN7
TOMM20L	ENST00000557754.1 link	n.184A>C		non_coding_transcript_exon_variant	Exon 3 of 4	1		ENSP00000451683.1	G3V4A4
ENSG00000258378	ENST00000556734.1 link	n.374+8399A>C		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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000346

AC:

AN:

1447098

Hom.:

Cov.:

AF XY:

0.00000556

AC XY:

AN XY:

719786

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000669

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.0000134

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:

0.00

Gnomad4 OTH

AF:

0.00189

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 18, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.266A>C (p.E89A) alteration is located in exon 4 (coding exon 4) of the TOMM20L gene. This alteration results from a A to C substitution at nucleotide position 266, causing the glutamic acid (E) at amino acid position 89 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Benign

0.83

DEOGEN2

Benign

0.061

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.59

M_CAP

Benign

0.011

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.6

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-4.8

REVEL

Benign

0.14

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.051

Polyphen

0.89

Vest4

0.27

MutPred

0.43

Gain of MoRF binding (P = 0.0199);

MVP

0.099

MPC

1.0

ClinPred

0.98

GERP RS

4.8

Varity_R

0.51

gMVP

0.14

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over