chr22-20019469-A-C

Variant names:

• chr22-20019469-A-C
• rs1858770
• NM_001283106.3:c.-40+170A>C

Variant summary

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

The NM_001283106.3(TANGO2):​c.-40+170A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,260 control chromosomes in the GnomAD database, including 1,737 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 0.10 (1737 hom., cov: 33)
• Consequence: TANGO2 NM_001283106.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.559
• Publications: 6 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001283106.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANGO2	NM_001283106.3		c.-40+170A>C		intron	N/A	NP_001270035.1
	TANGO2	NM_001283179.3		c.-40+2277A>C		intron	N/A	NP_001270108.1
	TANGO2	NM_001322163.2		c.-40+170A>C		intron	N/A	NP_001309092.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANGO2	ENST00000401886.5	TSL:5	c.-40+2277A>C		intron	N/A	ENSP00000385662.1
	TANGO2	ENST00000432198.5	TSL:4	c.-40+170A>C		intron	N/A	ENSP00000413850.1
	TANGO2	ENST00000471707.5	TSL:5	n.179+2277A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15777 AN: 152142 Hom.: 1724 Cov.: 33

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0912

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.0884

Gnomad SAS AF: 0.0914

Gnomad FIN AF: 0.0407

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0202

Gnomad OTH AF: 0.0926

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

GnomAD4 genome AF: 0.104 AC: 15824 AN: 152260 Hom.: 1737 Cov.: 33 AF XY: 0.105 AC XY: 7793 AN XY: 74446

African (AFR) AF: 0.271 AC: 11241 AN: 41512

American (AMR) AF: 0.0912 AC: 1396 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0522 AC: 181 AN: 3470

East Asian (EAS) AF: 0.0882 AC: 458 AN: 5192

South Asian (SAS) AF: 0.0911 AC: 440 AN: 4830

European-Finnish (FIN) AF: 0.0407 AC: 432 AN: 10612

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0202 AC: 1373 AN: 68020

Other (OTH) AF: 0.0922 AC: 195 AN: 2116

Alfa AF: 0.0590 Hom.: 1220

Bravo AF: 0.114

Asia WGS AF: 0.104 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.8
DANN	Benign	0.42
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1858770; hg19: chr22-20006992;