Variant 1-161229087-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032174.6(TOMM40L):c.919G>A(p.Val307Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TOMM40L
NM_032174.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.899

Variant links:

Genes affected

TOMM40L (HGNC:25756): (translocase of outer mitochondrial membrane 40 like) Predicted to enable protein transmembrane transporter activity. Predicted to be involved in protein import into mitochondrial matrix. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

TOMM40L 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=0.22310263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOMM40L	NM_032174.6 linkuse as main transcript	c.919G>A	p.Val307Met	missense_variant	10/10	ENST00000367988.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOMM40L	ENST00000367988.8 linkuse as main transcript	c.919G>A	p.Val307Met	missense_variant	10/10	2	NM_032174.6	P1	Q969M1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251444

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135880

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2022

The c.919G>A (p.V307M) alteration is located in exon 10 (coding exon 9) of the TOMM40L gene. This alteration results from a G to A substitution at nucleotide position 919, causing the valine (V) at amino acid position 307 to be replaced by a methionine (M). 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

0.23

BayesDel_addAF

Uncertain

0.072

BayesDel_noAF

Benign

-0.13

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

D;.;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.62

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

0.98

.;D;D

Vest4

0.41

MutPred

0.41

.;Gain of disorder (P = 0.0771);Gain of disorder (P = 0.0771);

MVP

0.17

MPC

1.3

ClinPred

0.84

GERP RS

5.2

Varity_R

0.46

gMVP

0.65

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