Variant chr15-73873714-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153356.3(TBC1D21):c.5C>T(p.Thr2Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,454,408 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TBC1D21
NM_153356.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.34

Variant links:

Genes affected

TBC1D21 (HGNC:28536): (TBC1 domain family member 21) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D21	NM_153356.3 linkuse as main transcript	c.5C>T	p.Thr2Ile	missense_variant	1/11	ENST00000300504.7	NP_699187.1	Q8IYX1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TBC1D21	ENST00000300504.7 linkuse as main transcript	c.5C>T	p.Thr2Ile	missense_variant	1/11	1	NM_153356.3	ENSP00000300504.2	Q8IYX1-1
TBC1D21	ENST00000535547.6 linkuse as main transcript	c.5C>T	p.Thr2Ile	missense_variant	1/10	1		ENSP00000439325.2	Q8IYX1-2
TBC1D21	ENST00000562056.1 linkuse as main transcript	c.5C>T	p.Thr2Ile	missense_variant	1/10	5		ENSP00000457096.1	H3BTA9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000167

AC:

AN:

239054

Hom.:

AF XY:

0.0000155

AC XY:

AN XY:

128916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000222

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:

0.00000413

AC:

AN:

1454408

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

722754

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

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

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

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

Nov 10, 2024

The c.5C>T (p.T2I) alteration is located in exon 1 (coding exon 1) of the TBC1D21 gene. This alteration results from a C to T substitution at nucleotide position 5, causing the threonine (T) at amino acid position 2 to be replaced by an isoleucine (I). 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

0.33

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0040

.;T;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.52

T;T;T

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.44

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.54

MutPred

0.30

Loss of glycosylation at T2 (P = 0.0018);Loss of glycosylation at T2 (P = 0.0018);Loss of glycosylation at T2 (P = 0.0018);

MVP

0.41

MPC

0.83

ClinPred

0.70

GERP RS

5.6

Varity_R

0.28

gMVP

0.49

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