Variant chr19-49881457-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000221543.10(TBC1D17):c.509G>T(p.Arg170Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000304 in 1,609,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R170C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

TBC1D17
ENST00000221543.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

Variant links:

Genes affected

TBC1D17 (HGNC:25699): (TBC1 domain family member 17) Predicted to enable GTPase activator activity. Involved in retrograde transport, endosome to Golgi. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40605682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TBC1D17	NM_024682.3 linkuse as main transcript	c.509G>T	p.Arg170Leu	missense_variant	5/17	ENST00000221543.10	NP_078958.2
TBC1D17	NM_001168222.2 linkuse as main transcript	c.410G>T	p.Arg137Leu	missense_variant	4/16		NP_001161694.1
TBC1D17	XM_047439444.1 linkuse as main transcript	c.509G>T	p.Arg170Leu	missense_variant	5/16		XP_047295400.1
TBC1D17	XM_011527317.4 linkuse as main transcript	c.509G>T	p.Arg170Leu	missense_variant	5/14		XP_011525619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D17	ENST00000221543.10 linkuse as main transcript	c.509G>T	p.Arg170Leu	missense_variant	5/17	1	NM_024682.3	ENSP00000221543	P1	Q9HA65-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152176

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:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000569

AC:

AN:

245902

Hom.:

AF XY:

0.0000746

AC XY:

AN XY:

133968

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000426

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000316

AC:

AN:

1457224

Hom.:

Cov.:

AF XY:

0.0000455

AC XY:

AN XY:

725158

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000511

Gnomad4 FIN exome

AF:

0.0000201

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000577

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

Feb 22, 2023

The c.509G>T (p.R170L) alteration is located in exon 5 (coding exon 5) of the TBC1D17 gene. This alteration results from a G to T substitution at nucleotide position 509, causing the arginine (R) at amino acid position 170 to be replaced by a leucine (L). 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

0.31

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.020

MetaRNN

Benign

0.41

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-4.0

D;D

REVEL

Benign

0.17

Sift

Uncertain

0.022

D;D

Sift4G

Uncertain

0.041

D;D

Vest4

0.60

MutPred

0.45

Loss of MoRF binding (P = 0.0067);.;

MVP

0.51

MPC

0.72

ClinPred

0.77

GERP RS

5.5

gMVP

0.67

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