dbSNP rs780743160: TIMM10B:p.Gly102Ser (chr11-6482213-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_012192.4(TIMM10B):c.304G>A(p.Gly102Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000499 in 1,604,304 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

TIMM10B
NM_012192.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.35

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=0.08029458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMM10B	NM_012192.4 link	c.304G>A	p.Gly102Ser	missense_variant	Exon 3 of 3	ENST00000254616.11	NP_036324.1	Q9Y5J6B2R4A9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMM10B	ENST00000254616.11 link	c.304G>A	p.Gly102Ser	missense_variant	Exon 3 of 3	1	NM_012192.4	ENSP00000254616.6		Q9Y5J6
ENSG00000283977	ENST00000640959.1 link	n.304G>A		non_coding_transcript_exon_variant	Exon 3 of 5	4		ENSP00000491841.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000831

AC:

AN:

240774

Hom.:

AF XY:

0.00000760

AC XY:

AN XY:

131624

show subpopulations

Gnomad AFR exome

AF:

0.000133

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1452106

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722112

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0035

T;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.63

M_CAP

Benign

0.0050

MetaRNN

Benign

0.080

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.

PrimateAI

Benign

0.43

PROVEAN

Benign

0.56

N;N

REVEL

Benign

0.055

Sift

Benign

0.20

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.0

B;.

Vest4

0.13

MutPred

0.17

Gain of phosphorylation at G102 (P = 0.0068);.;

MVP

0.25

MPC

0.094

ClinPred

0.054

GERP RS

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.051

gMVP

0.54

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over