14-58408574-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_207377.3(TOMM20L):c.451C>A(p.Pro151Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TOMM20L
NM_207377.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.315

Publications

0 publications found

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:

TIMM9 (HGNC:11819): (translocase of inner mitochondrial membrane 9) TIMM9 belongs to a family of evolutionarily conserved proteins that are organized in heterooligomeric complexes in the mitochondrial intermembrane space. These proteins mediate the import and insertion of hydrophobic membrane proteins into the mitochondrial inner membrane.[supplied by OMIM, Apr 2004]

TIMM9 links:

ENSG00000258378 (HGNC:):

ENSG00000258378 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207377.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TOMM20L	NM_207377.3	MANE Select	c.451C>A	p.Pro151Thr	missense	Exon 5 of 5	NP_997260.1	Q6UXN7
TIMM9	NM_012460.4	MANE Select	c.*460G>T		3_prime_UTR	Exon 6 of 6	NP_036592.1	Q9Y5J7
TIMM9	NM_001304485.2		c.*460G>T		3_prime_UTR	Exon 5 of 5	NP_001291414.1	Q9Y5J7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TOMM20L	ENST00000360945.7	TSL:1 MANE Select	c.451C>A	p.Pro151Thr	missense	Exon 5 of 5	ENSP00000354204.2	Q6UXN7
TIMM9	ENST00000395159.7	TSL:1 MANE Select	c.*460G>T		3_prime_UTR	Exon 6 of 6	ENSP00000378588.2	Q9Y5J7
TOMM20L	ENST00000557754.1	TSL:1	n.*144C>A		non_coding_transcript_exon	Exon 4 of 4	ENSP00000451683.1	G3V4A4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251310

AF XY:

0.00000736

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461690

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727150

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111918

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

9.1

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.012

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.47

M_CAP

Benign

0.0060

MetaRNN

Benign

0.056

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

0.32

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.2

REVEL

Benign

0.079

Sift

Benign

0.17

Sift4G

Benign

0.11

Polyphen

0.28

Vest4

0.075

MutPred

0.24

Gain of phosphorylation at P151 (P = 0.0248)

MVP

0.081

MPC

0.73

ClinPred

0.090

GERP RS

1.1

Varity_R

0.049

gMVP

0.10

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.21

Position offset: -45

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over