22-46896592-A-G

Variant names:

• chr22-46896592-A-G
• rs738932
• NM_014346.5:c.900+1746A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014346.5(TBC1D22A):​c.900+1746A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 151,960 control chromosomes in the GnomAD database, including 37,026 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 0.69 (37026 hom., cov: 31)
• Consequence: TBC1D22A NM_014346.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 3 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.744 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D22A	NM_014346.5	MANE Select	c.900+1746A>G		intron	N/A	NP_055161.1	Q8WUA7-1
	TBC1D22A	NM_001284304.2		c.810+1746A>G		intron	N/A	NP_001271233.1	A0A0A0MRY0
	TBC1D22A	NM_001284305.2		c.759+1746A>G		intron	N/A	NP_001271234.1	Q8WUA7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D22A	ENST00000337137.9	TSL:1 MANE Select	c.900+1746A>G		intron	N/A	ENSP00000336724.4	Q8WUA7-1
	TBC1D22A	ENST00000380995.5	TSL:1	c.810+1746A>G		intron	N/A	ENSP00000370383.2	A0A0A0MRY0
	TBC1D22A	ENST00000355704.7	TSL:1	c.666+1746A>G		intron	N/A	ENSP00000347932.3	Q8WUA7-2

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105416 AN: 151840 Hom.: 37012 Cov.: 31

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.863

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.694 AC: 105477 AN: 151960 Hom.: 37026 Cov.: 31 AF XY: 0.692 AC XY: 51364 AN XY: 74278

African (AFR) AF: 0.582 AC: 24080 AN: 41390

American (AMR) AF: 0.691 AC: 10564 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2940 AN: 3468

East Asian (EAS) AF: 0.667 AC: 3446 AN: 5166

South Asian (SAS) AF: 0.685 AC: 3290 AN: 4800

European-Finnish (FIN) AF: 0.726 AC: 7669 AN: 10568

Middle Eastern (MID) AF: 0.863 AC: 252 AN: 292

European-Non Finnish (NFE) AF: 0.750 AC: 50964 AN: 67968

Other (OTH) AF: 0.727 AC: 1532 AN: 2108

Alfa AF: 0.740 Hom.: 123979

Bravo AF: 0.687

Asia WGS AF: 0.668 AC: 2320 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.56
PhyloP100		-2.3
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: rs738932; hg19: chr22-47292488;