Variant 17-79940998-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019020.4(TBC1D16):c.2165C>A(p.Ala722Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000618 in 1,455,942 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

TBC1D16
NM_019020.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.20

Variant links:

Genes affected

TBC1D16 (HGNC:28356): (TBC1 domain family member 16) Enables GTPase activator activity. Involved in regulation of receptor recycling. Located in cytosol and early endosome. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D16 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18537045).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D16	NM_019020.4 linkuse as main transcript	c.2165C>A	p.Ala722Glu	missense_variant	12/12	ENST00000310924.7	NP_061893.2	Q8TBP0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TBC1D16	ENST00000310924.7 linkuse as main transcript	c.2165C>A	p.Ala722Glu	missense_variant	12/12	1	NM_019020.4	ENSP00000309794.2	Q8TBP0-1
TBC1D16	ENST00000340848.11 linkuse as main transcript	c.1079C>A	p.Ala360Glu	missense_variant	8/8	1		ENSP00000341517.7	Q8TBP0-2
TBC1D16	ENST00000576768.5 linkuse as main transcript	c.1040C>A	p.Ala347Glu	missense_variant	8/8	1		ENSP00000461522.1	Q8TBP0-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000211

AC:

AN:

237006

Hom.:

AF XY:

0.0000232

AC XY:

AN XY:

129310

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000206

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000941

Gnomad OTH exome

AF:

0.000346

GnomAD4 exome

AF:

0.00000618

AC:

AN:

1455942

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723842

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000832

GnomAD4 genome

Cov.:

Alfa

AF:

0.000174

Hom.:

ExAC

AF:

0.0000248

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

Dec 01, 2022

The c.2165C>A (p.A722E) alteration is located in exon 12 (coding exon 11) of the TBC1D16 gene. This alteration results from a C to A substitution at nucleotide position 2165, causing the alanine (A) at amino acid position 722 to be replaced by a glutamic acid (E). 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

0.21

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Benign

0.86

DEOGEN2

Benign

0.013

T;.;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.040

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;.;.

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.97

N;.;N

REVEL

Benign

0.24

Sift

Benign

0.45

T;.;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.066

B;.;.

Vest4

0.38

MutPred

0.22

Gain of solvent accessibility (P = 0.0097);.;.;

MVP

0.41

MPC

0.31

ClinPred

0.35

GERP RS

4.8

Varity_R

0.15

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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