rs5766691

chr22-47136753-A-Gchr22-47136753-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014346.5(TBC1D22A):c.1425+25150A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,164 control chromosomes in the GnomAD database, including 40,983 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.73 (40983 hom., cov: 34)
• Consequence: TBC1D22A NM_014346.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D22A	NM_014346.5	c.1425+25150A>G		intron_variant		ENST00000337137.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D22A	ENST00000337137.9	c.1425+25150A>G		intron_variant		1	NM_014346.5	P1

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111088 AN: 152046 Hom.: 40940 Cov.: 34

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.701

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.731 AC: 111192 AN: 152164 Hom.: 40983 Cov.: 34 AF XY: 0.741 AC XY: 55117 AN XY: 74398

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.967

Gnomad4 SAS AF: 0.861

Gnomad4 FIN AF: 0.807

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.704

Alfa AF: 0.722 Hom.: 6877

Bravo AF: 0.727

Asia WGS AF: 0.901 AC: 3130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.52
Dann	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs5766691; hg19: chr22-47532396;