22-20065259-C-T

Variant names:

• chr22-20065259-C-T
• rs367450
• NM_152906.7:c.*597C>T

Variant summary

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

The NM_152906.7(TANGO2):​c.*597C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,066 control chromosomes in the GnomAD database, including 15,370 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 0.44 (15367 hom., cov: 32)
  • Exomes 𝑓: 0.21 (3 hom.)
• Consequence: TANGO2 NM_152906.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813
• Publications: 7 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ENSG00000236540 (HGNC:41096):

ENSG00000268292 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152906.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANGO2	NM_152906.7	MANE Select	c.*597C>T		3_prime_UTR	Exon 9 of 9	NP_690870.3
	TANGO2	NM_001322141.2		c.*597C>T		3_prime_UTR	Exon 9 of 9	NP_001309070.1
	TANGO2	NM_001322142.2		c.*597C>T		3_prime_UTR	Exon 9 of 9	NP_001309071.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANGO2	ENST00000327374.9	TSL:1 MANE Select	c.*597C>T		3_prime_UTR	Exon 9 of 9	ENSP00000332721.4	Q6ICL3-1
	TANGO2	ENST00000401833.5	TSL:5	c.*597C>T		3_prime_UTR	Exon 9 of 9	ENSP00000384827.1	Q6ICL3-4
	TANGO2	ENST00000456048.5	TSL:2	c.*597C>T		3_prime_UTR	Exon 9 of 9	ENSP00000403645.2	Q6ICL3-4

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66934 AN: 151760 Hom.: 15339 Cov.: 32

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.438

GnomAD4 exome AF: 0.208 AC: 40 AN: 192 Hom.: 3 Cov.: 0 AF XY: 0.200 AC XY: 18 AN XY: 90

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.417 AC: 5 AN: 12

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.188 AC: 30 AN: 160

Other (OTH) AF: 0.250 AC: 3 AN: 12

GnomAD4 genome AF: 0.441 AC: 67015 AN: 151874 Hom.: 15367 Cov.: 32 AF XY: 0.446 AC XY: 33103 AN XY: 74234

African (AFR) AF: 0.481 AC: 19923 AN: 41408

American (AMR) AF: 0.528 AC: 8068 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1338 AN: 3466

East Asian (EAS) AF: 0.728 AC: 3756 AN: 5160

South Asian (SAS) AF: 0.507 AC: 2436 AN: 4804

European-Finnish (FIN) AF: 0.399 AC: 4208 AN: 10542

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25939 AN: 67898

Other (OTH) AF: 0.440 AC: 926 AN: 2104

Alfa AF: 0.367 Hom.: 7436

Bravo AF: 0.454

Asia WGS AF: 0.567 AC: 1968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.54
PhyloP100		-0.81
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: rs367450; hg19: chr22-20052782;