Variant 6-37284388-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000373491.3(TBC1D22B):c.725G>A(p.Arg242Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

TBC1D22B
ENST00000373491.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60

Variant links:

Genes affected

TBC1D22B (HGNC:21602): (TBC1 domain family member 22B) Enables 14-3-3 protein binding activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D22B links:

TBC1D22B (HGNC:):

TBC1D22B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D22B	NM_017772.4 linkuse as main transcript	c.725G>A	p.Arg242Gln	missense_variant	6/13	ENST00000373491.3	NP_060242.2	Q9NU19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D22B	ENST00000373491.3 linkuse as main transcript	c.725G>A	p.Arg242Gln	missense_variant	6/13	1	NM_017772.4	ENSP00000362590.3		Q9NU19

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

250334

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135344

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461130

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726886

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

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

Jan 25, 2023

The c.725G>A (p.R242Q) alteration is located in exon 6 (coding exon 6) of the TBC1D22B gene. This alteration results from a G to A substitution at nucleotide position 725, causing the arginine (R) at amino acid position 242 to be replaced by a glutamine (Q). 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

0.15

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.30

Eigen

Pathogenic

0.93

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.037

MetaRNN

Pathogenic

0.86

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.31

Sift

Benign

0.21

Sift4G

Benign

0.15

Polyphen

1.0

Vest4

0.87

MutPred

0.65

Loss of MoRF binding (P = 0.0504);

MVP

0.81

MPC

1.4

ClinPred

0.72

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.62

gMVP

0.87

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