Variant chr22-46793719-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014346.5(TBC1D22A):c.338C>T(p.Thr113Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00798 in 1,610,722 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0081 ( 78 hom. )

Consequence

TBC1D22A
NM_014346.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.274

Variant links:

Genes affected

TBC1D22A (HGNC:1309): (TBC1 domain family member 22A) Enables 14-3-3 protein binding activity and protein homodimerization activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D22A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035664141).

BP6

Variant 22-46793719-C-T is Benign according to our data. Variant chr22-46793719-C-T is described in ClinVar as [Benign]. Clinvar id is 777312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D22A	NM_014346.5 linkuse as main transcript	c.338C>T	p.Thr113Met	missense_variant	3/13	ENST00000337137.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D22A	ENST00000337137.9 linkuse as main transcript	c.338C>T	p.Thr113Met	missense_variant	3/13	1	NM_014346.5	P1	Q8WUA7-1

Frequencies

GnomAD3 genomes

AF:

0.00701

AC:

1067

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00292

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00569

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0243

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00850

Gnomad OTH

AF:

0.00767

GnomAD3 exomes

AF:

0.00751

AC:

1801

AN:

239730

Hom.:

AF XY:

0.00760

AC XY:

999

AN XY:

131454

show subpopulations

Gnomad AFR exome

AF:

0.00229

Gnomad AMR exome

AF:

0.00431

Gnomad ASJ exome

AF:

0.000308

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000858

Gnomad FIN exome

AF:

0.0254

Gnomad NFE exome

AF:

0.00955

Gnomad OTH exome

AF:

0.00845

GnomAD4 exome

AF:

0.00808

AC:

11788

AN:

1458428

Hom.:

Cov.:

AF XY:

0.00793

AC XY:

5752

AN XY:

725384

show subpopulations

Gnomad4 AFR exome

AF:

0.00269

Gnomad4 AMR exome

AF:

0.00467

Gnomad4 ASJ exome

AF:

0.000269

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00109

Gnomad4 FIN exome

AF:

0.0257

Gnomad4 NFE exome

AF:

0.00865

Gnomad4 OTH exome

AF:

0.00711

GnomAD4 genome

AF:

0.00700

AC:

1066

AN:

152294

Hom.:

Cov.:

AF XY:

0.00751

AC XY:

559

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00291

Gnomad4 AMR

AF:

0.00569

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0243

Gnomad4 NFE

AF:

0.00850

Gnomad4 OTH

AF:

0.00759

Alfa

AF:

0.00723

Hom.:

Bravo

AF:

0.00544

ESP6500AA

AF:

0.00137

AC:

ESP6500EA

AF:

0.00642

AC:

ExAC

AF:

0.00742

AC:

896

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00671

EpiControl

AF:

0.00767

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.25

DANN

Benign

0.92

DEOGEN2

Benign

0.0075

T;T;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.78

T;T;T;T;T

MetaRNN

Benign

0.0036

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

.;N;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.56

.;N;N;N;N

REVEL

Benign

0.036

Sift

Benign

0.11

.;T;T;T;T

Sift4G

Benign

0.11

T;T;T;T;T

Polyphen

0.90, 0.74, 0.61

.;P;P;P;.

Vest4

0.15

MVP

0.21

MPC

0.47

ClinPred

0.0065

GERP RS

-8.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.012

gMVP

0.17

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