22-20042355-T-C

Variant names:

• chr22-20042355-T-C
• rs374225
• NM_152906.7:c.57-1000T>C

Variant summary

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

The NM_001322141.2(TANGO2):​c.180-1000T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,978 control chromosomes in the GnomAD database, including 13,869 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 0.42 (13869 hom., cov: 31)
• Consequence: TANGO2 NM_001322141.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 8 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322141.2. 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.57-1000T>C		intron	N/A	NP_690870.3
	TANGO2	NM_001322141.2		c.180-1000T>C		intron	N/A	NP_001309070.1
	TANGO2	NM_001322142.2		c.57-1000T>C		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.57-1000T>C		intron	N/A	ENSP00000332721.4
	TANGO2	ENST00000401833.5	TSL:5	c.180-1000T>C		intron	N/A	ENSP00000384827.1
	TANGO2	ENST00000456048.5	TSL:2	c.180-1000T>C		intron	N/A	ENSP00000403645.2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63501 AN: 151860 Hom.: 13839 Cov.: 31

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.418 AC: 63587 AN: 151978 Hom.: 13869 Cov.: 31 AF XY: 0.423 AC XY: 31441 AN XY: 74272

African (AFR) AF: 0.404 AC: 16736 AN: 41440

American (AMR) AF: 0.520 AC: 7929 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1354 AN: 3472

East Asian (EAS) AF: 0.709 AC: 3663 AN: 5170

South Asian (SAS) AF: 0.510 AC: 2456 AN: 4818

European-Finnish (FIN) AF: 0.398 AC: 4202 AN: 10562

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25930 AN: 67958

Other (OTH) AF: 0.422 AC: 890 AN: 2110

Alfa AF: 0.373 Hom.: 5029

Bravo AF: 0.429

Asia WGS AF: 0.549 AC: 1905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.39
PhyloP100		-1.9
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: rs374225; hg19: chr22-20029878;