chr22-20054086-C-T

Variant names:

• chr22-20054086-C-T
• rs366148
• NM_152906.7:c.380+535C>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.380+535C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0666 in 282,944 control chromosomes in the GnomAD database, including 704 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 0.061 (329 hom., cov: 33)
  • Exomes 𝑓: 0.073 (375 hom.)
• Consequence: TANGO2 NM_152906.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0985 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.380+535C>T		intron	N/A	NP_690870.3
	TANGO2	NM_001322141.2		c.503+535C>T		intron	N/A	NP_001309070.1
	TANGO2	NM_001322142.2		c.380+535C>T		intron	N/A	NP_001309071.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANGO2	ENST00000327374.9	TSL:1 MANE Select	c.380+535C>T		intron	N/A	ENSP00000332721.4	Q6ICL3-1
	TANGO2	ENST00000401833.5	TSL:5	c.503+535C>T		intron	N/A	ENSP00000384827.1	Q6ICL3-4
	TANGO2	ENST00000456048.5	TSL:2	c.503+535C>T		intron	N/A	ENSP00000403645.2	Q6ICL3-4

Frequencies

GnomAD3 genomes AF: 0.0612 AC: 9312 AN: 152208 Hom.: 327 Cov.: 33

Gnomad AFR AF: 0.0572

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0366

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.0566

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0695

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.0588

GnomAD4 exome AF: 0.0730 AC: 9535 AN: 130618 Hom.: 375 Cov.: 0 AF XY: 0.0765 AC XY: 5422 AN XY: 70838

African (AFR) AF: 0.0525 AC: 137 AN: 2610

American (AMR) AF: 0.0358 AC: 165 AN: 4604

Ashkenazi Jewish (ASJ) AF: 0.0802 AC: 234 AN: 2918

East Asian (EAS) AF: 0.0553 AC: 207 AN: 3740

South Asian (SAS) AF: 0.108 AC: 2906 AN: 27026

European-Finnish (FIN) AF: 0.0678 AC: 463 AN: 6826

Middle Eastern (MID) AF: 0.0563 AC: 26 AN: 462

European-Non Finnish (NFE) AF: 0.0648 AC: 4929 AN: 76080

Other (OTH) AF: 0.0737 AC: 468 AN: 6352

GnomAD4 genome AF: 0.0612 AC: 9315 AN: 152326 Hom.: 329 Cov.: 33 AF XY: 0.0614 AC XY: 4575 AN XY: 74484

African (AFR) AF: 0.0572 AC: 2380 AN: 41578

American (AMR) AF: 0.0365 AC: 559 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0775 AC: 269 AN: 3470

East Asian (EAS) AF: 0.0565 AC: 293 AN: 5186

South Asian (SAS) AF: 0.106 AC: 512 AN: 4824

European-Finnish (FIN) AF: 0.0695 AC: 738 AN: 10620

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0648 AC: 4405 AN: 68022

Other (OTH) AF: 0.0572 AC: 121 AN: 2114

Alfa AF: 0.0681 Hom.: 103

Bravo AF: 0.0567

Asia WGS AF: 0.0920 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.63
DANN	Benign	0.48
PhyloP100		-1.6
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: rs366148; hg19: chr22-20041609;