rs9606213

Variant names:

• chr22-20029448-G-A
• rs9606213
• NM_152906.7:c.-39-7312G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152906.7(TANGO2):​c.-39-7312G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,166 control chromosomes in the GnomAD database, including 13,544 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 0.39 (13544 hom., cov: 32)
• Consequence: TANGO2 NM_152906.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.444
• Publications: 5 publications found

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]

TANGO2 Gene-Disease associations (from GenCC):

• recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TANGO2	NM_152906.7	c.-39-7312G>A		intron_variant	Intron 1 of 8	ENST00000327374.9	NP_690870.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TANGO2	ENST00000327374.9	c.-39-7312G>A		intron_variant	Intron 1 of 8	1	NM_152906.7	ENSP00000332721.4

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58671 AN: 152048 Hom.: 13542 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.386 AC: 58690 AN: 152166 Hom.: 13544 Cov.: 32 AF XY: 0.384 AC XY: 28595 AN XY: 74386

African (AFR) AF: 0.147 AC: 6102 AN: 41530

American (AMR) AF: 0.397 AC: 6074 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2004 AN: 3470

East Asian (EAS) AF: 0.133 AC: 690 AN: 5184

South Asian (SAS) AF: 0.504 AC: 2425 AN: 4816

European-Finnish (FIN) AF: 0.511 AC: 5410 AN: 10578

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34344 AN: 67988

Other (OTH) AF: 0.425 AC: 895 AN: 2106

Alfa AF: 0.425 Hom.: 3029

Bravo AF: 0.360

Asia WGS AF: 0.302 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		0.44
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: rs9606213; hg19: chr22-20016971;