Variant 3-17214335-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001349074.2(TBC1D5):c.1690G>A(p.Val564Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000329 in 1,613,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

TBC1D5
NM_001349074.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.74

Variant links:

Genes affected

TBC1D5 (HGNC:19166): (TBC1 domain family member 5) Enables AP-2 adaptor complex binding activity and retromer complex binding activity. Involved in several processes, including macroautophagy; positive regulation of receptor internalization; and retrograde transport, endosome to Golgi. Located in Golgi apparatus; autophagosome; and endosome membrane. Part of retromer complex. Colocalizes with AP-2 adaptor complex and Atg1/ULK1 kinase complex. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D5 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011286885).

BP6

Variant 3-17214335-C-T is Benign according to our data. Variant chr3-17214335-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2267378.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D5	NM_001349074.2 linkuse as main transcript	c.1690G>A	p.Val564Ile	missense_variant	19/23	ENST00000696125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D5	ENST00000696125.1 linkuse as main transcript	c.1690G>A	p.Val564Ile	missense_variant	19/23		NM_001349074.2	P2	Q92609-2

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000514

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000468

AC:

117

AN:

249764

Hom.:

AF XY:

0.000563

AC XY:

AN XY:

135024

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000205

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.000219

Gnomad SAS exome

AF:

0.000559

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000708

Gnomad OTH exome

AF:

0.000657

GnomAD4 exome

AF:

0.000323

AC:

472

AN:

1460890

Hom.:

Cov.:

AF XY:

0.000345

AC XY:

251

AN XY:

726734

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000314

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.000674

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000310

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.000381

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000584

Hom.:

Bravo

AF:

0.000393

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.00147

EpiControl

AF:

0.00125

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.29

DEOGEN2

Benign

0.0030

T;T;.;T

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.069

M_CAP

Benign

0.0085

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.0

N;N;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

0.18

N;N;N;N

REVEL

Benign

0.069

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;B;.;B

Vest4

0.13

MVP

0.11

MPC

0.11

ClinPred

0.0060

GERP RS

3.5

Varity_R

0.017

gMVP

0.10

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