chr22-46898271-A-G

Variant names:

• chr22-46898271-A-G
• rs762646
• NM_014346.5:c.900+3425A>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+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
• 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=-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 rank	MANE	Protein	UniProt
TBC1D22A	NM_014346.5	c.900+3425A>G		intron_variant	Intron 7 of 12	ENST00000337137.9	NP_055161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D22A	ENST00000337137.9	c.900+3425A>G		intron_variant	Intron 7 of 12	1	NM_014346.5	ENSP00000336724.4

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

African (AFR) AF: 0.955 AC: 39620 AN: 41502

American (AMR) AF: 0.793 AC: 12123 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2967 AN: 3470

East Asian (EAS) AF: 0.688 AC: 3551 AN: 5164

South Asian (SAS) AF: 0.689 AC: 3325 AN: 4824

European-Finnish (FIN) AF: 0.736 AC: 7778 AN: 10564

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51705 AN: 68004

Other (OTH) AF: 0.822 AC: 1737 AN: 2114

Alfa AF: 0.779 Hom.: 11390

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
PhyloP100		-2.0
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: rs762646; hg19: chr22-47294167;