6-37282314-C-T

Variant names:

• chr6-37282314-C-T
• rs146761886
• NM_017772.4:c.551C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017772.4(TBC1D22B):​c.551C>T​(p.Thr184Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T184N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TBC1D22B NM_017772.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.13

Genes affected

TBC1D22B (HGNC:21602): (TBC1 domain family member 22B) Enables 14-3-3 protein binding 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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33095437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D22B	NM_017772.4	c.551C>T	p.Thr184Ile	missense_variant	Exon 4 of 13	ENST00000373491.3	NP_060242.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D22B	ENST00000373491.3	c.551C>T	p.Thr184Ile	missense_variant	Exon 4 of 13	1	NM_017772.4	ENSP00000362590.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250418 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135358

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461298 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726896

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.11
Sift	Benign	0.14	T
Sift4G	Benign	0.10	T
Polyphen		0.054	B
Vest4		0.60
MutPred		0.29		Loss of phosphorylation at T184 (P = 0.0474);
MVP		0.58
MPC		0.73
ClinPred		0.28	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.44

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: rs146761886; hg19: chr6-37250090;