22-46899981-T-C

Position:

• chr22-46899981-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D22A	NM_014346.5	c.900+5135T>C		intron_variant		ENST00000337137.9	NP_055161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D22A	ENST00000337137.9	c.900+5135T>C		intron_variant		1	NM_014346.5	ENSP00000336724.4

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

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.849

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.750

Gnomad4 OTH AF: 0.737

Alfa AF: 0.718 Hom.: 9384

Bravo AF: 0.703

Asia WGS AF: 0.659 AC: 2292 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	0.20
DANN	Benign	0.28

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: rs6009041; hg19: chr22-47295877;