rs9627642

chr22-47004963-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.1201+7254T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 151,834 control chromosomes in the GnomAD database, including 520 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 0.048 (520 hom., cov: 32)
• Consequence: TBC1D22A NM_014346.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D22A	NM_014346.5	c.1201+7254T>C		intron_variant		ENST00000337137.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D22A	ENST00000337137.9	c.1201+7254T>C		intron_variant		1	NM_014346.5	P1

Frequencies

GnomAD3 genomes AF: 0.0481 AC: 7302 AN: 151720 Hom.: 517 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00471

Gnomad OTH AF: 0.0392

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

GnomAD4 genome AF: 0.0483 AC: 7329 AN: 151834 Hom.: 520 Cov.: 32 AF XY: 0.0462 AC XY: 3427 AN XY: 74208

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0191

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.00254

Gnomad4 NFE AF: 0.00471

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0452 Hom.: 67

Bravo AF: 0.0537

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.4
Dann	Benign	0.40
RBP_binding_hub_radar		0.91
RBP_regulation_power_radar		2.0

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: rs9627642; hg19: chr22-47400859;