Variant 11-6481532-C-G 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_012192.4(TIMM10B):c.16C>G(p.Gln6Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,459,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.000015 ( 0 hom. )

Consequence

TIMM10B
NM_012192.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.54

Variant links:

Genes affected

TIMM10B (HGNC:4022): (translocase of inner mitochondrial membrane 10B) FXC1, or TIMM10B, 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]

TIMM10B links:

ENSG00000283977 (HGNC:):

ENSG00000283977 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=0.13910905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMM10B	NM_012192.4 link	c.16C>G	p.Gln6Glu	missense_variant	1/3	ENST00000254616.11	NP_036324.1	Q9Y5J6B2R4A9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMM10B	ENST00000254616.11 link	c.16C>G	p.Gln6Glu	missense_variant	1/3	1	NM_012192.4	ENSP00000254616.6		Q9Y5J6
ENSG00000283977	ENST00000640959.1 link	n.16C>G		non_coding_transcript_exon_variant	1/5	4		ENSP00000491841.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000411

AC:

AN:

243286

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131800

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000294

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1459672

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

725890

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

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:

0.0000189

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Jun 21, 2023

The c.16C>G (p.Q6E) alteration is located in exon 1 (coding exon 1) of the TIMM10B gene. This alteration results from a C to G substitution at nucleotide position 16, causing the glutamine (Q) at amino acid position 6 to be replaced by a glutamic acid (E). 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

0.053

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0054

T;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.016

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

N;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.090

N;N

REVEL

Benign

0.16

Sift

Benign

1.0

T;D

Sift4G

Benign

0.99

T;D

Polyphen

0.0060

B;.

Vest4

0.45

MutPred

0.47

Loss of MoRF binding (P = 0.0497);Loss of MoRF binding (P = 0.0497);

MVP

0.47

MPC

0.11

ClinPred

0.16

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.21

gMVP

0.35

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