22-20019469-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001283106.3(TANGO2):​c.-40+170A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,272 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 (0 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: 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANGO2	NM_001283106.3		c.-40+170A>T		intron	N/A	NP_001270035.1	Q6ICL3-1
	TANGO2	NM_001283179.3		c.-40+2277A>T		intron	N/A	NP_001270108.1	Q6ICL3-2
	TANGO2	NM_001322163.2		c.-40+170A>T		intron	N/A	NP_001309092.1	Q6ICL3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANGO2	ENST00000852305.1		c.-40+2277A>T		intron	N/A	ENSP00000522364.1
	TANGO2	ENST00000957774.1		c.-40+2277A>T		intron	N/A	ENSP00000627833.1
	TANGO2	ENST00000401886.5	TSL:5	c.-40+2277A>T		intron	N/A	ENSP00000385662.1	Q6ICL3-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152154 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152272 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74456

African (AFR) AF: 0.00 AC: 0 AN: 41518

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 1220

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.6
DANN	Benign	0.53
PhyloP100		0.56

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;