Variant 22-46793850-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_014346.5(TBC1D22A):c.460+9G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000687 in 1,546,540 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00082 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00067 ( 13 hom. )

Consequence

TBC1D22A
NM_014346.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.30

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 22-46793850-G-C is Benign according to our data. Variant chr22-46793850-G-C is described in ClinVar as [Benign]. Clinvar id is 721878.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000821 (125/152330) while in subpopulation EAS AF= 0.0207 (107/5176). AF 95% confidence interval is 0.0175. There are 5 homozygotes in gnomad4. There are 73 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D22A	NM_014346.5 linkuse as main transcript	c.460+9G>C		intron_variant		ENST00000337137.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D22A	ENST00000337137.9 linkuse as main transcript	c.460+9G>C		intron_variant		1	NM_014346.5	P1	Q8WUA7-1

Frequencies

GnomAD3 genomes

AF:

0.000828

AC:

126

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0208

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00227

AC:

326

AN:

143876

Hom.:

AF XY:

0.00196

AC XY:

153

AN XY:

78072

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000506

Gnomad ASJ exome

AF:

0.00177

Gnomad EAS exome

AF:

0.0275

Gnomad SAS exome

AF:

0.000248

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00156

GnomAD4 exome

AF:

0.000672

AC:

937

AN:

1394210

Hom.:

Cov.:

AF XY:

0.000633

AC XY:

436

AN XY:

689270

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000320

Gnomad4 ASJ exome

AF:

0.00176

Gnomad4 EAS exome

AF:

0.0219

Gnomad4 SAS exome

AF:

0.000180

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000148

Gnomad4 OTH exome

AF:

0.000884

GnomAD4 genome

AF:

0.000821

AC:

125

AN:

152330

Hom.:

Cov.:

AF XY:

0.000980

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.0207

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000407

Hom.:

Bravo

AF:

0.000907

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.0

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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