22-46894823-A-G

Position:

• chr22-46894823-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014346.5(TBC1D22A):​c.877A>G​(p.Ile293Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TBC1D22A NM_014346.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92

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]

ACMG classification

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=0.11480552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D22A	NM_014346.5	c.877A>G	p.Ile293Val	missense_variant	7/13	ENST00000337137.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D22A	ENST00000337137.9	c.877A>G	p.Ile293Val	missense_variant	7/13	1	NM_014346.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2021

The c.877A>G (p.I293V) alteration is located in exon 7 (coding exon 7) of the TBC1D22A gene. This alteration results from a A to G substitution at nucleotide position 877, causing the isoleucine (I) at amino acid position 293 to be replaced by a valine (V). 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	0.081
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.4
DANN	Benign	0.50
DEOGEN2	Benign	0.027	T;T;T;.;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.80	T;T;T;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.51	T
REVEL	Benign	0.072
Sift4G	Benign	0.12	T;T;T;T;T
Polyphen		0.0, 0.0010	.;B;B;B;.
Vest4		0.21
MutPred		0.48		.;Loss of methylation at K297 (P = 0.1237);.;.;.;
MVP		0.068
MPC		0.33
ClinPred		0.070	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.065
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-47290719;