dbSNP rs1408274456: TOMM40:p.Ser49Gly (chr19-44891560-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_001128917.2(TOMM40):c.145A>G(p.Ser49Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S49R) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TOMM40
NM_001128917.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0430

Publications

0 publications found

Variant links:

Genes affected

TOMM40 (HGNC:18001): (translocase of outer mitochondrial membrane 40) The protein encoded by this gene is localized in the outer membrane of the mitochondria. It is the channel-forming subunit of the translocase of the mitochondrial outer membrane (TOM) complex that is essential for import of protein precursors into mitochondria. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]

TOMM40 links:

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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;

BP6

Variant 19-44891560-A-G is Benign according to our data. Variant chr19-44891560-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3460060.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128917.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TOMM40	NM_001128917.2	MANE Select	c.145A>G	p.Ser49Gly	missense	Exon 1 of 9	NP_001122389.1	O96008-1
TOMM40	NM_001128916.2		c.145A>G	p.Ser49Gly	missense	Exon 2 of 10	NP_001122388.1	O96008-1
TOMM40	NM_006114.3		c.145A>G	p.Ser49Gly	missense	Exon 2 of 10	NP_006105.1	O96008-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TOMM40	ENST00000426677.7	TSL:1 MANE Select	c.145A>G	p.Ser49Gly	missense	Exon 1 of 9	ENSP00000410339.1	O96008-1
TOMM40	ENST00000252487.9	TSL:1	c.145A>G	p.Ser49Gly	missense	Exon 2 of 10	ENSP00000252487.4	O96008-1
TOMM40	ENST00000405636.6	TSL:1	c.145A>G	p.Ser49Gly	missense	Exon 2 of 10	ENSP00000385184.2	O96008-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1285336

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

631626

African (AFR)

AF:

0.00

AC:

AN:

26212

American (AMR)

AF:

0.00

AC:

AN:

24018

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22252

East Asian (EAS)

AF:

0.00

AC:

AN:

27812

South Asian (SAS)

AF:

0.00

AC:

AN:

69358

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32654

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3752

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1026720

Other (OTH)

AF:

0.00

AC:

AN:

52558

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.060

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.081

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.53

M_CAP

Benign

0.022

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.043

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.98

REVEL

Benign

0.027

Sift

Benign

0.42

Sift4G

Benign

0.48

Polyphen

0.0

Vest4

0.026

MutPred

0.15

Loss of glycosylation at S49 (P = 0.006)

MVP

0.068

MPC

0.049

ClinPred

0.032

GERP RS

0.83

PromoterAI

0.073

Neutral

(source)

Varity_R

0.031

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.26

Position offset: 0

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