Genetic Variant TBC1D12:p.Ile33Met (chr10-94402712-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015188.2(TBC1D12):c.99C>G(p.Ile33Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000977 in 1,433,352 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: not found (cov: 33)

Exomes 𝑓: 0.0000098 ( 0 hom. )

Consequence

TBC1D12
NM_015188.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.613

Publications

0 publications found

Variant links:

Genes affected

TBC1D12 (HGNC:29082): (TBC1 domain family member 12) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity; intracellular protein transport; and regulation of autophagosome assembly. Predicted to be active in autophagosome and recycling endosome. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D12 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;

BP4

Computational evidence support a benign effect (MetaRNN=0.12434453).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015188.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D12	NM_015188.2	MANE Select	c.99C>G	p.Ile33Met	missense	Exon 1 of 13	NP_056003.1	O60347

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBC1D12	ENST00000225235.5	TSL:1 MANE Select	c.99C>G	p.Ile33Met	missense	Exon 1 of 13	ENSP00000225235.4	O60347
TBC1D12	ENST00000971288.1		c.99C>G	p.Ile33Met	missense	Exon 1 of 12	ENSP00000641347.1
TBC1D12	ENST00000904400.1		c.99C>G	p.Ile33Met	missense	Exon 1 of 12	ENSP00000574459.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000156

AC:

AN:

192118

AF XY:

0.0000284

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000977

AC:

AN:

1433352

Hom.:

Cov.:

AF XY:

0.0000155

AC XY:

AN XY:

710664

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32670

American (AMR)

AF:

0.00

AC:

AN:

41242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25512

East Asian (EAS)

AF:

0.00

AC:

AN:

38222

South Asian (SAS)

AF:

0.0000722

AC:

AN:

83082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49988

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5616

European-Non Finnish (NFE)

AF:

0.00000729

AC:

AN:

1097818

Other (OTH)

AF:

0.00

AC:

AN:

59202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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

Cov.:

ExAC

AF:

0.0000169

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

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.0097

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.42

M_CAP

Benign

0.065

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

PhyloP100

-0.61

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.010

REVEL

Benign

0.12

Sift

Benign

0.11

Sift4G

Uncertain

0.0060

Polyphen

0.95

Vest4

0.15

MutPred

0.26

Gain of MoRF binding (P = 0.0842)

MVP

0.33

MPC

0.50

ClinPred

0.21

GERP RS

-0.58

PromoterAI

-0.0059

Neutral

(source)

Varity_R

0.072

gMVP

0.048

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over