chr22-20055981-G-T

Position:

• chr22-20055981-G-T

Variant summary

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

The ENST00000327374.9(TANGO2):​c.419G>T​(p.Arg140Leu) 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. 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. R140Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TANGO2 ENST00000327374.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11

Genes affected

TANGO2 (HGNC:25439): (transport and golgi organization 2 homolog) This gene belongs to the transport and Golgi organization family, whose members are predicted to play roles in secretory protein loading in the endoplasmic reticulum. Depletion of this gene in Drosophila S2 cells causes fusion of the Golgi with the ER. In mouse tissue culture cells, this protein co-localizes with a mitochondrially targeted mCherry protein and displays very low levels of co-localization with Golgi and peroxisomes. Allelic variants of this gene are associated with rhabdomyolysis, metabolic crises with encephalopathy, and cardiac arrhythmia. [provided by RefSeq, Apr 2016]

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=0.3474139).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TANGO2	NM_152906.7	c.419G>T	p.Arg140Leu	missense_variant	6/9	ENST00000327374.9	NP_690870.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TANGO2	ENST00000327374.9	c.419G>T	p.Arg140Leu	missense_variant	6/9	1	NM_152906.7	ENSP00000332721	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	.;.;.;.;T;.;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D;D;D;D;D;.;D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.35	T;T;T;T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.0	.;.;.;.;M;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.5	D;.;.;D;D;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.029	D;.;.;D;D;T;D
Sift4G	Uncertain	0.022	D;D;D;D;T;D;D
Polyphen		0.81	.;.;.;.;P;.;.
Vest4		0.52
MVP		0.42
MPC		0.54
ClinPred		0.99	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs142442293; hg19: chr22-20043504;