Genetic Variant NM_001146213.3:c.35T>C (chr12-71872074-T-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001146213.3(TBC1D15):c.35T>C(p.Ile12Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TBC1D15
NM_001146213.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.91

Publications

0 publications found

Variant links:

Genes affected

TBC1D15 (HGNC:25694): (TBC1 domain family member 15) This gene encodes a member of the Ras-like proteins in brain-GTPase activating protein superfamily that share a conserved Tre-2/Bub2/Cdc16 domain. The encoded protein interacts with Ras-like protein in brain 5A and may function as a regulator of intracellular trafficking. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

TBC1D15 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.82

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146213.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBC1D15	NM_001146213.3	MANE Select	c.35T>C	p.Ile12Thr	missense	Exon 2 of 17	NP_001139685.2	Q8TC07-2
TBC1D15	NM_022771.6		c.35T>C	p.Ile12Thr	missense	Exon 2 of 18	NP_073608.4
TBC1D15	NM_001385848.1		c.35T>C	p.Ile12Thr	missense	Exon 2 of 17	NP_001372777.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBC1D15	ENST00000485960.7	TSL:1 MANE Select	c.35T>C	p.Ile12Thr	missense	Exon 2 of 17	ENSP00000420678.2	Q8TC07-2
TBC1D15	ENST00000550746.5	TSL:1	c.35T>C	p.Ile12Thr	missense	Exon 2 of 18	ENSP00000448182.1	Q8TC07-1
TBC1D15	ENST00000491063.5	TSL:1	c.-263T>C		5_prime_UTR	Exon 3 of 11	ENSP00000418091.1	C9JA93

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1337644

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

664400

African (AFR)

AF:

0.00

AC:

AN:

28538

American (AMR)

AF:

0.00

AC:

AN:

29398

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23148

East Asian (EAS)

AF:

0.00

AC:

AN:

35272

South Asian (SAS)

AF:

0.00

AC:

AN:

66308

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50810

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5382

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1043694

Other (OTH)

AF:

0.00

AC:

AN:

55094

GnomAD4 genome

Cov.:

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

0.21

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.062

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.013

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

5.9

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.0

REVEL

Benign

0.26

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.020

Polyphen

0.55

Vest4

0.82

MutPred

0.77

Loss of catalytic residue at I12 (P = 0.0396)

MVP

0.52

MPC

0.46

ClinPred

0.92

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.46

Mutation Taster

=72/28

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over