rs5766691

Variant names:

• chr22-47136753-A-G
• rs5766691
• NM_014346.5:c.1425+25150A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-47136753-A-G
• chr22-47136753-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014346.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D22A	NM_014346.5	MANE Select	c.1425+25150A>G		intron	N/A	NP_055161.1
	TBC1D22A	NM_001284304.2		c.1335+25150A>G		intron	N/A	NP_001271233.1
	TBC1D22A	NM_001284305.2		c.1284+25150A>G		intron	N/A	NP_001271234.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D22A	ENST00000337137.9	TSL:1 MANE Select	c.1425+25150A>G		intron	N/A	ENSP00000336724.4
	TBC1D22A	ENST00000380995.5	TSL:1	c.1335+25150A>G		intron	N/A	ENSP00000370383.2
	TBC1D22A	ENST00000355704.7	TSL:1	c.1191+25150A>G		intron	N/A	ENSP00000347932.3

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

African (AFR) AF: 0.710 AC: 29470 AN: 41492

American (AMR) AF: 0.776 AC: 11878 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2368 AN: 3470

East Asian (EAS) AF: 0.967 AC: 4997 AN: 5166

South Asian (SAS) AF: 0.861 AC: 4158 AN: 4832

European-Finnish (FIN) AF: 0.807 AC: 8568 AN: 10612

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47428 AN: 67974

Other (OTH) AF: 0.704 AC: 1489 AN: 2114

Alfa AF: 0.716 Hom.: 58310

Bravo AF: 0.727

Asia WGS AF: 0.901 AC: 3130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.48
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5766691; hg19: chr22-47532396;