chr11-6481527-A-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_012192.4(TIMM10B):c.11A>C(p.Gln4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,579,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

TIMM10B
NM_012192.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0450

Publications

1 publications found

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:

ARFIP2 (HGNC:17160): (ADP ribosylation factor interacting protein 2) Enables several functions, including GTP-dependent protein binding activity; membrane curvature sensor activity; and phosphatidylinositol-4-phosphate binding activity. Involved in actin cytoskeleton organization. Located in cell cortex; ruffle; and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARFIP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06712952).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012192.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TIMM10B	NM_012192.4	MANE Select	c.11A>C	p.Gln4Pro	missense	Exon 1 of 3	NP_036324.1	Q9Y5J6
ARFIP2	NM_001376558.2	MANE Select	c.-339T>G		upstream_gene	N/A	NP_001363487.1	P53365-1
ARFIP2	NM_001242854.3		c.-339T>G		upstream_gene	N/A	NP_001229783.1	A0A087X1E4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TIMM10B	ENST00000254616.11	TSL:1 MANE Select	c.11A>C	p.Gln4Pro	missense	Exon 1 of 3	ENSP00000254616.6	Q9Y5J6
TIMM10B	ENST00000528908.1	TSL:1	n.27A>C		non_coding_transcript_exon	Exon 1 of 2
ENSG00000283977	ENST00000640959.1	TSL:4	n.11A>C		non_coding_transcript_exon	Exon 1 of 5	ENSP00000491841.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151842

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000582

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000632

AC:

AN:

237510

AF XY:

0.0000854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000509

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000470

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1427190

Hom.:

Cov.:

AF XY:

0.0000324

AC XY:

AN XY:

709558

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32464

American (AMR)

AF:

0.00

AC:

AN:

43390

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25382

East Asian (EAS)

AF:

0.000736

AC:

AN:

39422

South Asian (SAS)

AF:

0.0000240

AC:

AN:

83260

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00000920

AC:

AN:

1086770

Other (OTH)

AF:

0.0000338

AC:

AN:

59182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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

AF:

0.0000263

AC:

AN:

151958

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000584

AC:

AN:

5140

South Asian (SAS)

AF:

0.000208

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67976

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000828

AC:

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

0.063

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.40

CADD

Benign

6.1

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.0065

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.59

M_CAP

Benign

0.0022

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

0.045

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.59

REVEL

Benign

0.13

Sift

Benign

0.26

Sift4G

Benign

0.29

Polyphen

0.91

Vest4

0.36

MutPred

0.52

Loss of helix (P = 0.0167)

MVP

0.50

MPC

0.13

ClinPred

0.059

GERP RS

2.8

PromoterAI

0.0079

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.23

gMVP

0.59

Mutation Taster

=93/7

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over