chr22-47004963-T-C

Variant names:

• chr22-47004963-T-C
• rs9627642
• NM_014346.5:c.1201+7254T>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.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
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 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.1201+7254T>C		intron	N/A	NP_055161.1
	TBC1D22A	NM_001284304.2		c.1111+7254T>C		intron	N/A	NP_001271233.1
	TBC1D22A	NM_001284305.2		c.1060+7254T>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.1201+7254T>C		intron	N/A	ENSP00000336724.4
	TBC1D22A	ENST00000380995.5	TSL:1	c.1111+7254T>C		intron	N/A	ENSP00000370383.2
	TBC1D22A	ENST00000355704.7	TSL:1	c.967+7254T>C		intron	N/A	ENSP00000347932.3

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

African (AFR) AF: 0.158 AC: 6539 AN: 41304

American (AMR) AF: 0.0191 AC: 292 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.0141 AC: 68 AN: 4818

European-Finnish (FIN) AF: 0.00254 AC: 27 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00471 AC: 320 AN: 67886

Other (OTH) AF: 0.0388 AC: 82 AN: 2112

Alfa AF: 0.0490 Hom.: 75

Bravo AF: 0.0537

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.40
PhyloP100		-1.3
RBP_binding_hub_radar		0.91
RBP_regulation_power_radar		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: rs9627642; hg19: chr22-47400859;