22-46899981-T-C

Variant names:

• chr22-46899981-T-C
• rs6009041
• NM_014346.5:c.900+5135T>C

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+5135T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 151,764 control chromosomes in the GnomAD database, including 38,286 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 0.71 (38286 hom., cov: 30)
• Consequence: TBC1D22A NM_014346.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.82
• Publications: 2 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.745 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.900+5135T>C		intron	N/A	NP_055161.1
	TBC1D22A	NM_001284304.2		c.810+5135T>C		intron	N/A	NP_001271233.1
	TBC1D22A	NM_001284305.2		c.759+5135T>C		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.900+5135T>C		intron	N/A	ENSP00000336724.4
	TBC1D22A	ENST00000380995.5	TSL:1	c.810+5135T>C		intron	N/A	ENSP00000370383.2
	TBC1D22A	ENST00000355704.7	TSL:1	c.666+5135T>C		intron	N/A	ENSP00000347932.3

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107426 AN: 151646 Hom.: 38271 Cov.: 30

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.812

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.708 AC: 107489 AN: 151764 Hom.: 38286 Cov.: 30 AF XY: 0.705 AC XY: 52302 AN XY: 74140

African (AFR) AF: 0.632 AC: 26091 AN: 41280

American (AMR) AF: 0.696 AC: 10626 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2942 AN: 3466

East Asian (EAS) AF: 0.658 AC: 3398 AN: 5162

South Asian (SAS) AF: 0.686 AC: 3299 AN: 4808

European-Finnish (FIN) AF: 0.725 AC: 7590 AN: 10470

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.750 AC: 50996 AN: 67998

Other (OTH) AF: 0.737 AC: 1552 AN: 2106

Alfa AF: 0.721 Hom.: 15017

Bravo AF: 0.703

Asia WGS AF: 0.659 AC: 2292 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	0.20
DANN	Benign	0.28
PhyloP100		-3.8
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: rs6009041; hg19: chr22-47295877;