rs771782230

Variant names:

• chr6-37279370-T-A
• rs771782230
• NM_017772.4:c.180T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-37279370-T-A
• chr6-37279370-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017772.4(TBC1D22B):​c.180T>A​(p.His60Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H60L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBC1D22B NM_017772.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05171776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D22B	NM_017772.4	c.180T>A	p.His60Gln	missense_variant	Exon 3 of 13	ENST00000373491.3	NP_060242.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D22B	ENST00000373491.3	c.180T>A	p.His60Gln	missense_variant	Exon 3 of 13	1	NM_017772.4	ENSP00000362590.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	6.5
DANN	Benign	0.71
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.39	N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	1.6	N
REVEL	Uncertain	0.33
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.34
MutPred		0.33		Gain of helix (P = 0.062);
MVP		0.68
MPC		0.63
ClinPred		0.050	T
GERP RS		-0.069
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.092
gMVP		0.33

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: rs771782230; hg19: chr6-37247146;