rs762646

Positions:

• chr22-46898271-A-G

Variant summary

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

The NM_014346.5(TBC1D22A):​c.900+3425A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 152,142 control chromosomes in the GnomAD database, including 51,076 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 0.81 (51076 hom., cov: 31)
• Consequence: TBC1D22A NM_014346.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D22A	NM_014346.5	c.900+3425A>G		intron_variant		ENST00000337137.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D22A	ENST00000337137.9	c.900+3425A>G		intron_variant		1	NM_014346.5	P1

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123696 AN: 152024 Hom.: 51018 Cov.: 31

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.814 AC: 123817 AN: 152142 Hom.: 51076 Cov.: 31 AF XY: 0.809 AC XY: 60168 AN XY: 74380

Gnomad4 AFR AF: 0.955

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.822

Alfa AF: 0.775 Hom.: 11047

Bravo AF: 0.824

Asia WGS AF: 0.715 AC: 2488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.57
DANN	Benign	0.37

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: rs762646; hg19: chr22-47294167;