Genetic Variant ENST00000377773.9:c.179C>T (chr9-37592354-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000377773.9(TOMM5):c.179C>T(p.Pro60Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TOMM5
ENST00000377773.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.969

Publications

1 publications found

Variant links:

Genes affected

TOMM5 (HGNC:31369): (translocase of outer mitochondrial membrane 5) Predicted to be involved in protein targeting to mitochondrion. Located in mitochondrion. Part of mitochondrial outer membrane translocase complex. [provided by Alliance of Genome Resources, Apr 2022]

TOMM5 links:

ENSG00000256966 (HGNC:):

ENSG00000256966 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06933394).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000377773.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TOMM5	NM_001001790.3	MANE Select	c.121+58C>T		intron	N/A	NP_001001790.1	Q8N4H5-1
TOMM5	NM_001134484.2		c.179C>T	p.Pro60Leu	missense	Exon 1 of 2	NP_001127956.1	Q8N4H5-2
TOMM5	NM_001134485.2		c.179C>T	p.Pro60Leu	missense	Exon 1 of 2	NP_001127957.1	Q8N4H5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TOMM5	ENST00000377773.9	TSL:1	c.179C>T	p.Pro60Leu	missense	Exon 1 of 2	ENSP00000367004.5	Q8N4H5-3
TOMM5	ENST00000321301.7	TSL:1 MANE Select	c.121+58C>T		intron	N/A	ENSP00000313584.6	Q8N4H5-1
ENSG00000256966	ENST00000537239.2	TSL:5	n.116C>T		non_coding_transcript_exon	Exon 1 of 3	ENSP00000457849.1	H3BUX3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000409

AC:

AN:

244596

AF XY:

0.00000754

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459086

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725516

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33422

American (AMR)

AF:

0.00

AC:

AN:

44404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39580

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53246

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110728

Other (OTH)

AF:

0.00

AC:

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

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

0.099

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.4

(source)

DANN

Benign

0.90

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.55

M_CAP

Benign

0.0058

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.0

PhyloP100

-0.97

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.98

REVEL

Benign

0.020

Sift

Pathogenic

0.0

Sift4G

Benign

0.090

Vest4

0.096

MutPred

0.34

Gain of stability (P = 0.0076)

MVP

0.068

MPC

1.1

ClinPred

0.46

GERP RS

-2.5

PromoterAI

-0.070

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.036

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over